[go: up one dir, main page]

CN111662977A - Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit - Google Patents

Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit Download PDF

Info

Publication number
CN111662977A
CN111662977A CN202010615201.8A CN202010615201A CN111662977A CN 111662977 A CN111662977 A CN 111662977A CN 202010615201 A CN202010615201 A CN 202010615201A CN 111662977 A CN111662977 A CN 111662977A
Authority
CN
China
Prior art keywords
gene
seq
nucleotide sequence
probe
primer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202010615201.8A
Other languages
Chinese (zh)
Inventor
张燕
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
XI AN SPIRIT SANITARY CENTRAL
Original Assignee
XI AN SPIRIT SANITARY CENTRAL
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by XI AN SPIRIT SANITARY CENTRAL filed Critical XI AN SPIRIT SANITARY CENTRAL
Priority to CN202010615201.8A priority Critical patent/CN111662977A/en
Publication of CN111662977A publication Critical patent/CN111662977A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/16—Primer sets for multiplex assays

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

The invention discloses a gene probe, a chip, a kit and application thereof for detecting metabolic influence of an anti-mental medicament, wherein the gene probe chip is a gene chip for selecting the anti-mental medicament and comprises a group of probes and a group of multiplex PCR primer groups, the gene chip can specifically detect the genetic condition of sugar, lipid metabolism capability and weight change of a patient, is beneficial to a doctor to know the individual genetic characteristics of the patient in advance, selects the anti-mental disorder medicament in a targeted manner, better avoids the occurrence of detectable adverse reaction, prevents the self-stopping medicament caused by the remarkable change of the sugar, lipid metabolism capability and weight, avoids the relapse of the mental disorder and realizes the individualized anti-mental disorder medicament treatment. Therefore, the detection kit based on the gene chip adopts the sugar and lipid metabolism and effect target gene chip for detection, combines retrospective investigation and actual case observation, and has the advantages of good sensitivity of detection results, high accuracy, strong practicability, convenient sampling and easy popularization and use.

Description

Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit
Technical Field
The invention belongs to the technical field of biological medicines, and relates to a gene probe, a chip, a kit and application thereof for detecting metabolic influence of an anti-psychotropic drug.
Background
Gene detection refers to a technique for detecting DNA by blood, other body fluids or cells (oral mucosal cells or other tissue cells). The method is a method for extracting DNA in cells and amplifying related genes by taking peripheral venous blood or other tissue cells of a detected person, detecting DNA molecular information in the cells of the detected person through specific instruments and equipment, and analyzing whether the gene type, the gene defect and the expression function contained in the cells are normal or not, so that people can know the gene information of themselves, and can determine the cause of disease, predict the risk of a certain disease of a body or the risk of adverse reaction when using a therapeutic drug. Thereby utilizing a targeted means to prevent or improve the possible effects of the related genes. By gene detection, SNP typing of an individual can be clarified, and the genetic characteristics of the individual and appropriate therapeutic drugs can be judged by interpreting the SNP sites.
The anti-mental disorder drug (short for anti-mental drug) has close influence on the weight, fat and sugar metabolism of patients in the long-term treatment process and has significant difference on the degree of weight increase and reduction of individuals with different SNP loci genotyping. The drug treatment period of the first patient with mental disorder is as long as 5 years, and the patients usually stop taking the drugs automatically due to obesity and dyslipidemia in the period. After a while, the recurrence needs to be prolonged to 8-10 years after the secondary medication. The age of onset of schizophrenia is 14-16 years, the critical period of treatment enters the age of marriage and pregnancy, and the serious change of body weight and the abnormal blood fat cause the direct reason of drug withdrawal. However, a gene detection kit that can cause body weight change using an anti-psychotic drug has not been found so far.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a gene probe, a chip, a kit and application thereof for detecting the metabolic influence of an anti-psychotropic drug, wherein the kit has the advantages of good sensitivity, high accuracy and strong practicability, and can quickly detect the weight influence, fat metabolism and sugar metabolism conditions of individual characteristics.
In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:
the invention discloses a gene probe group for detecting metabolism influence of an anti-psychotropic drug, which is used for carrying out combined specific amplification on a nucleic acid fragment containing c.102T > C site of HTR2A gene, rs1414334C > G site of HTR2C gene, -1131T > C site of APOA5 gene and rs1000940A > G site of RABEP1 gene;
the kit specifically comprises eight probes from 1 to 8, wherein:
the nucleotide sequence of the probe 1 is shown as SEQ.ID.NO. 1;
the nucleotide sequence of the probe 2 is shown as SEQ.ID.NO. 2;
the nucleotide sequence of the probe 3 is shown as SEQ.ID.NO. 3;
the nucleotide sequence of the probe 4 is shown as SEQ.ID.NO. 4;
the nucleotide sequence of the probe 5 is shown as SEQ.ID.NO. 5;
the nucleotide sequence of the probe 6 is shown as SEQ.ID.NO. 6;
the nucleotide sequence of the probe 7 is shown as SEQ.ID.NO. 7;
the nucleotide sequence of the probe 8 is shown in SEQ.ID.NO. 8.
Preferably, the gene chip consists of the gene probe group and a multiplex PCR primer group;
the multiplex PCR primer group is used for carrying out combined specific detection on the c.102T > C site of the HTR2A gene, the rs1414334C > G site of the HTR2C gene, the-1131T > C site of the APOA5 gene and the rs1000940A > G genotype of the RABEP1 gene.
Further preferably, the multiplex PCR primer set B includes eight primers from primer 1 to primer 8, wherein:
the nucleotide sequence of the primer 1 is shown as SEQ.ID.NO. 9;
the nucleotide sequence of the primer 2 is shown as SEQ.ID.NO. 10;
the nucleotide sequence of the primer 3 is shown as SEQ.ID.NO. 11;
the nucleotide sequence of the primer 4 is shown as SEQ.ID.NO. 12;
the nucleotide sequence of the primer 5 is shown as SEQ.ID.NO. 13;
the nucleotide sequence of the primer 6 is shown as SEQ.ID.NO. 14;
the nucleotide sequence of the primer 7 is shown as SEQ.ID.NO. 15;
the nucleotide sequence of the primer 8 is shown in SEQ ID No. 16.
Preferably, the probes in the gene chip are immobilized on a solid support.
Further preferably, the solid phase carrier is a nylon membrane, a nitrocellulose membrane, a quartz glass plate or polystyrene.
The invention also discloses a gene detection kit for the metabolic influence of the psychotropic drugs, which comprises the gene chip.
Preferably, the gene detection kit further comprises a hybridization solution and an eluent.
More preferably, the hybridization solution contains formamide with a mass concentration of 0.5mol/L and sodium dodecyl sulfate with a mass concentration of 0.002mol/L, and is diluted with pure water according to the hybridization reaction system before use.
Further eluent is absolute ethyl alcohol.
The invention also discloses application of the gene detection kit in screening the anti-mental drugs influencing individual metabolism.
Compared with the prior art, the invention has the following beneficial effects:
the invention discloses a gene probe chip for detecting metabolism influence of anti-psychotropic drugs and a detection kit based on the gene probe chip, wherein the gene probe chip is a gene chip for selecting anti-psychotropic drugs, and comprises a group of probes and a group of multiplex PCR primer groups, and probe group sequences contained in the gene probe chip are used for specifically amplifying nucleic acid fragments containing c.102T > C site of HTR2A gene, rs1414334C > G site of HTR2C gene, -1131T > C site of APOA5 gene and rs1000940A > G site of RABEP1 gene; the primer group contained in the kit is used for specifically detecting c.102T > C site of HTR2A gene, rs1414334C > G site of HTR2C gene, -1131T > C site of APOA5 gene and rs1000940A > G genotype of RABEP1 gene. The influence of the sites on sugar and lipid metabolism capability and weight significance change is reported in separate documents before, but the verification ratio is low under non-combination conditions, and influence interactivity cannot be reflected.
Therefore, the gene chip can specifically detect the sugar and lipid metabolism capability and weight change gene condition of a patient, is beneficial to a doctor to know the individual genetic characteristics of the patient in advance, selects the anti-mental disorder medicine in a targeted manner, better avoids the occurrence of detectable adverse reaction, prevents the self-stopping medicine caused by the significant change of the sugar and lipid metabolism capability and the weight, avoids the relapse of mental disorder and realizes the individualized anti-mental disorder medicine treatment. Therefore, the detection kit based on the gene chip adopts the sugar and lipid metabolism and effect target gene chip for detection, combines retrospective investigation and actual case observation, and has the advantages of good sensitivity of detection results, high accuracy, strong practicability, convenient sampling and easy popularization and use.
Detailed Description
In order to make the technical solution of the present invention better understood by those skilled in the art, the technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It is noted that the terms "comprises" and "comprising," and any variations thereof, in the description and claims of this invention, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
The invention is described in further detail below:
a gene detection kit for causing sugar, lipid metabolism ability and weight change by using an anti-mental disorder medicament comprises a sugar, lipid metabolism and effect target gene chip, wherein the sugar, lipid metabolism and effect target gene chip comprises a probe group A and a multiple PCR primer group 1;
the probe set is used for specifically amplifying nucleic acid fragments containing c.102T > C site of HTR2A gene, rs1414334C > G site of HTR2C gene, -1131T > C site of APOA5 gene and rs1000940A > G site of RABEP1 gene;
the multiplex PCR primer group is used for specifically detecting c.102T > C locus of HTR2A gene, rs1414334C > G locus of HTR2C gene, -1131T > C locus of APOA5 gene and rs1000940A > G genotype of RABEP1 gene.
The multiplex PCR primer group comprises a primer 1, a primer 2, a primer 3, a primer 4, a primer 5, a primer 6, a primer 7 and a primer 8 (shown as SEQ.ID.NO. 9-SEQ.ID.NO. 16 in a nucleotide sequence table), wherein the sequences of the primers are as follows:
(1) the primer 1: 5'-CTCAACTACGAACTCCCTAATGCAA-3', respectively;
(2) the primer 2: 5'-CGACTGTCCAGTTAAATGCATCAGA-3', respectively;
(3) the primer 3: 5'-GATAAAATTGGCCTCATCTACC-3', respectively;
(4) the primer 4: 5'-CACTTGTCTAAGGGATTCTTGAG-3', respectively;
(5) the primer 5: 5'-CCCTGCGAGTGGAGTTCA-3', respectively;
(6) the primer 6: 5'-CTCTGAGCCCCAGGAACTG-3', respectively;
(7) the primer 7: 5'-TGTTGGCTCCCAACGTGCTGTGCTG-3', respectively;
(8) the primer 8: 5'-TACAGGGCAAAGACAAGGGTGAC-3', respectively;
the probe set comprises a probe 1, a probe 2, a probe 3, a probe 4, a probe 5, a probe 6, a probe 7 and a probe 8 (shown as SEQ.ID.NO. 1-SEQ.ID.NO. 8 in a nucleotide sequence table), and the sequences of the probes are as follows:
(1) the probe 1: 5'-CTTCTCCGGAGTTAAA-3', respectively;
(2) the probe 2 is: 5'-CTTCTCCAGAGTTAAA-3', respectively;
(3) the probe 3: 5'-GCTACCCTGTCTTGCTG-3', respectively;
(4) the probe 4 is: 5'-GCTACCCTCTCTTGCTG-3', respectively;
(5) the probe 5 is: 5'-AGCGAAAGTGAGATTT-3', respectively;
(6) the probe 6 is: 5'-AGCGAAAGTAAGATTT-3', respectively;
(7) the probe 7 is: 5'-GTGTTTTTAGTGCGTGC-3', respectively;
(8) the probe 8: 5'-GTGTTTTTGGTGCGTGC-3', respectively;
the probe set includes a plurality of probes, each of which is immobilized on a solid support. The solid phase carrier can be one of a nylon membrane, a nitrocellulose membrane, a quartz glass sheet and polystyrene.
The kit also comprises a hybridization solution and an eluent (absolute ethyl alcohol), wherein the hybridization solution contains formamide (with the mass concentration of 0.5mol/L) and sodium dodecyl sulfate (with the mass concentration of 0.002 mol/L).
Example 1
The drug effect evaluation is carried out on 422 cases of examined people when using anti-mental disorder drugs of amisulpride, aripiprazole, ziprasidone, olanzapine, quetiapine, risperidone and the like, the PANSS reduction rate is more than or equal to 30 percent and is determined to be effective, and the standard for evaluating the curative effect of other scales is referred to the standard. The total response rate was 77.3% for 422 patients with each genotype at the c.102t > C site of HTR2A gene, as shown in table 1. Wherein the response rate of patients with HTR2A gene c.102T > C site CC genotype is highest, and the response rate of patients treated by olanzapine for more than 28 days is 87.5%.
TABLE 1 drug Effect over treatment cycles
Figure BDA0002563508830000061
Considering that patients may have time problems with drug response during treatment, the time divisions listed in table 2 show that HTR2A has higher response rates for CC and CT genotypes when the treatment period is less than 28 days, consistent with table 1. However, when the treatment period is increased to be ≧ 28 days, the response rate of the TT genotype is increased to 80.9%, which indicates that patients with the TT genotype at the c.102T > C site of the HTR2A gene need longer treatment of antipsychotic drugs for effectiveness.
TABLE 2 drug Effect over different treatment cycles
Figure BDA0002563508830000071
Wherein 119 subjects were monitored for weight, patients with c.102t > C site C T genotype of HTR2A gene were on busulfate, aripiprazole, ziprasidone, olanzapine, quetiapine, risperidone, etc., the anti-psychotic drug, wherein olanzapine had the greatest effect on weight, and the user had a weight gain of > 7% accounting for 16.3% of patients with CT genotype, 3 of which occurred after more than 28 days of therapeutic drug use; aripiprazole users lost > 7% of their body weight in patients with CT genotype 13.6%, quetiapine users lost > 7% of their body weight in patients with CT genotype 9.5%. 11.4% of subjects with the TT genotype who have olanzapine users who have a weight gain of > 7% are those with the TT genotype who have a significant change in weight after more than 28 consecutive days of administration; risperidone users gained weight > 7% by 20% of patients with TT genotype; aripiprazole users had a weight loss of > 7% in patients with the TT genotype of 15.4%; in contrast, patients with CC genotype are not easy to cause weight change when treated by the anti-mental disorder medicament, and only 1 case of patients with weight gain of more than 7% appears in quetiapine users; wherein amisulpride and ziprasidone have little influence on the body weight of patients with various genotypes, and the change of more than 7 percent does not occur.
Therefore, when the kit is used, medicines such as amisulpride, aripiprazole, ziprasidone, olanzapine, quetiapine, risperidone and the like can be selected under the guidance of the c.102T > C site genotype of the HTR2A gene, so that the treatment effect can be improved, and meanwhile, the stable body weight can be kept.
Example 2
The weight, the blood fat, the blood sugar and the liver function of 100 examinees are monitored, when an anti-mental disorder drug amisulpride, aripiprazole, ziprasidone, olanzapine, quetiapine, risperidone and the like is used by a patient with the rs1414334C G site GG genotype of HTR2C gene, patients with aripiprazole, ziprasidone, amisulpride were not observed to gain body weight > 7%, the weight gain of users of the remaining drugs was mainly focused on this genotype, and 47.1% of patients after treatment developed different degrees of single-or multi-index abnormalities such as total fasting cholesterol (TC), Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Fasting Plasma Glucose (FPG), alanine Aminotransferase (ALT), and aspartate Aminotransferase (AST), with the largest number of cases treated with olanzapine and risperidone; quetiapine and aripiprazole treated patients had 3 cases with weight loss > 7%, while these 3 patients had varying degrees of abnormal liver function and abnormal apolipoprotein. And the abnormal rate of the indexes of the body weight and the metabolic syndrome of the patients with the CC genotype at the rs1414334C > G site with the HTR2C gene is only 6.7 percent.
Therefore, when the kit is used, drugs such as amisulpride, aripiprazole, ziprasidone, olanzapine, quetiapine, risperidone and the like can be selected under the guidance of the genotype of the locus rs1414334C > G of the HTR2C gene, so that the significant change of body weight and the occurrence of metabolic syndrome can be prevented.
Example 3
In 100 subjects, the TT genotype of the-1131T > C site with the APOA5 gene has stronger lipid metabolism capability, and retrospective analysis of medical records and drug use conditions shows that before treatment, patients have low abnormal rates of fasting Total Cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and are not easy to cause abnormal blood lipid indexes or metabolic syndrome due to the use of anti-psychotic drugs; the lipid metabolism ability of the examinees with the genotype of APOA5 gene-1131T > C site C is weaker, and after the examinees the same as 119 examinees in the example 1 are treated by the anti-mental disorder drug after treatment, 1 example has the conditions that the fasting LDL-C and TG are higher and the weight gain is obvious (the weight gain is more than 7 percent); 3 cases have high fasting TC, the weight gain is 3% -6%, retrospective analysis of medical history and drug use conditions shows that after the two genes in the example 1 and the example 2 are influenced and combined, the patient adopts anti-mental disorder drugs of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, paliperidone, risperidone, lithium and the like, and metabolic syndrome is more likely to occur; this is more evident in the subjects having the CC gene at the-1131T > C site of APOA5 gene.
Example 4
The rs1000940A > G site AA gene of RABEP1 gene has weaker sugar metabolism capability, and abnormal blood sugar level (26.9%) easily occurs when anti-mental disorder drugs of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, paliperidone, risperidone, lithium and the like are used; while the AG and GG genotypes have lower blood sugar concentration than those of AA genotype subjects, and can normally carry out sugar metabolism, and the subjects having the rs1000940A > G site G genotype of the RABEP1 gene have normal sugar metabolism capability among a plurality of subjects, and the subjects find that abnormal blood sugar level is not easy to occur when anti-mental disorder drugs are used in research (19.2%, compared with A genotype P < 0.05). Therefore, the examinee who possesses the rs1000940A > G site AA genotype of RABEP1 gene needs to select the anti-mental disorder drugs with low risk when using the anti-mental disorder drugs, such as: aripiprazole. In addition, the patients with mental disorder need to pay close attention to the blood sugar level, and the intake of 2 sugar is reasonably controlled to avoid the occurrence of diabetes.
Example 5
Comprehensive analysis is carried out on 114 patients with the 4 sites, and the proportion of sugar and lipid metabolism abnormality (increase or decrease has clinical significance) and the proportion of weight reduction or increase of > 7% of the patients with the c.102T > C mutation TT or CT genotype of the H TR2A gene, the rs1414334C > G site GG genotype of the HTR2C gene, the-1131T > C site GG genotype of the APOA5 gene and the rs1000940A > G site AG gene of the RABEP1 gene are all more than 60%. The abnormal ratio of TC, TG and LDL-C is more than 70%. Therefore, the kit formed by combining the four sites can be used for judging the possible influence of the medicament on metabolism and body weight before use, and avoiding sugar and lipid metabolism abnormality and large-scale body weight change.
Can help the mental disorder patients to individually select drugs, is beneficial to the long-term taking compliance of the chronic disease of the mental disorder and the individual health state of the patients, and can pertinently select proper drugs for treatment, prevent the self-stopping drug caused by the significant change of lipid metabolism ability and weight, and avoid the relapse of the mental disorder.
In summary, after reading the present disclosure, those skilled in the art can make various other corresponding changes without creative mental labor according to the technical solutions and concepts of the present disclosure, and all of them are within the protection scope of the present disclosure.
The above-mentioned contents are only for illustrating the technical idea of the present invention, and the protection scope of the present invention is not limited thereby, and any modification made on the basis of the technical idea of the present invention falls within the protection scope of the claims of the present invention.
Sequence listing
<110> mental health center of xi' an city
<120> gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application thereof
<160>16
<170>SIPOSequenceListing 1.0
<210>1
<211>16
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>1
cttctccgga gttaaa 16
<210>2
<211>16
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>2
cttctccaga gttaaa 16
<210>3
<211>17
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>3
gctaccctgt cttgctg 17
<210>4
<211>17
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>4
gctaccctct cttgctg 17
<210>5
<211>16
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>5
agcgaaagtg agattt 16
<210>6
<211>16
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>6
agcgaaagta agattt 16
<210>7
<211>17
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>7
gtgtttttag tgcgtgc 17
<210>8
<211>17
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>8
gtgtttttgg tgcgtgc 17
<210>9
<211>25
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>9
ctcaactacg aactccctaa tgcaa 25
<210>10
<211>25
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>10
cgactgtcca gttaaatgca tcaga 25
<210>11
<211>22
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>11
gataaaattg gcctcatcta cc 22
<210>12
<211>23
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>12
cacttgtcta agggattctt gag 23
<210>13
<211>18
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>13
ccctgcgagt ggagttca 18
<210>14
<211>19
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>14
ctctgagccc caggaactg 19
<210>15
<211>25
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>15
tgttggctcc caacgtgctg tgctg 25
<210>16
<211>23
<212>DNA
<213> Artificial Sequence (Artificial Sequence)
<400>16
tacagggcaa agacaagggt gac 23

Claims (10)

1. A gene probe group for detecting the metabolic influence of an anti-psychotropic drug is characterized in that the gene probe group is used for carrying out combined specific amplification on a nucleic acid fragment containing c.102T > C site of HTR2A gene, rs1414334C > G site of HTR2C gene, -1131T > C site of APOA5 gene and rs1000940A > G site of RABEP1 gene;
the kit specifically comprises eight probes from 1 to 8, wherein:
the nucleotide sequence of the probe 1 is shown as SEQ.ID.NO. 1;
the nucleotide sequence of the probe 2 is shown as SEQ.ID.NO. 2;
the nucleotide sequence of the probe 3 is shown as SEQ.ID.NO. 3;
the nucleotide sequence of the probe 4 is shown as SEQ.ID.NO. 4;
the nucleotide sequence of the probe 5 is shown as SEQ.ID.NO. 5;
the nucleotide sequence of the probe 6 is shown as SEQ.ID.NO. 6;
the nucleotide sequence of the probe 7 is shown as SEQ.ID.NO. 7;
the nucleotide sequence of the probe 8 is shown in SEQ.ID.NO. 8.
2. The gene chip for detecting the metabolic influence of an antipsychotic drug, according to claim 1, wherein the gene chip comprises the gene probe group and a multiplex PCR primer group;
the multiplex PCR primer group is used for carrying out combined specificity detection on c.102T > C locus of HTR2A gene, rs1414334C > G locus of HTR2C gene, -1131T > C locus of APOA5 gene and rs1000940A > G genotype of RABEP1 gene.
3. The gene chip of claim 2, wherein the multiplex PCR primer set comprises eight primers from primer 1 to primer 8, wherein:
the nucleotide sequence of the primer 1 is shown as SEQ.ID.NO. 9;
the nucleotide sequence of the primer 2 is shown as SEQ.ID.NO. 10;
the nucleotide sequence of the primer 3 is shown as SEQ.ID.NO. 11;
the nucleotide sequence of the primer 4 is shown as SEQ.ID.NO. 12;
the nucleotide sequence of the primer 5 is shown as SEQ.ID.NO. 13;
the nucleotide sequence of the primer 6 is shown as SEQ.ID.NO. 14;
the nucleotide sequence of the primer 7 is shown as SEQ.ID.NO. 15;
the nucleotide sequence of the primer 8 is shown in SEQ ID No. 16.
4. The gene chip of claim 2, wherein the probes of the gene chip are immobilized on a solid phase carrier.
5. The gene chip for detecting the metabolic influence of an antipsychotic drug according to claim 4, wherein the solid carrier is a nylon membrane, a nitrocellulose membrane, a quartz glass plate or polystyrene.
6. A gene detection kit for metabolic influence using an antipsychotic agent, which comprises the gene chip according to any one of claims 2 to 5.
7. The gene assaying kit for metabolic effects using an antipsychotic according to claim 6, further comprising a hybridization solution and an eluent.
8. The gene assaying kit for metabolic effects using an antipsychotic according to claim 7, wherein the hybridization solution contains formamide at a mass concentration of 0.5mol/L and sodium dodecyl sulfate at a mass concentration of 0.002mol/L, and is diluted with pure water in accordance with the hybridization reaction system before use.
9. The gene detection kit for metabolic effects using an antipsychotic according to claim 7, wherein the eluent is absolute ethanol.
10. Use of the gene detection kit according to any one of claims 7 to 9 for screening an anti-psychotic drug that affects the metabolism of an individual.
CN202010615201.8A 2020-06-30 2020-06-30 Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit Pending CN111662977A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010615201.8A CN111662977A (en) 2020-06-30 2020-06-30 Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010615201.8A CN111662977A (en) 2020-06-30 2020-06-30 Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit

Publications (1)

Publication Number Publication Date
CN111662977A true CN111662977A (en) 2020-09-15

Family

ID=72390709

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010615201.8A Pending CN111662977A (en) 2020-06-30 2020-06-30 Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit

Country Status (1)

Country Link
CN (1) CN111662977A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2810798C1 (en) * 2022-10-14 2023-12-28 Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр психиатрии и неврологии имени В.М. Бехтерева" (ФГБУ "НМИЦ ПН им. В.М. Бехтерева" Минздрава России) Method of selecting treatment tactics for patients with antipsychotic-induced extrapyramidal disorders

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008144940A1 (en) * 2007-05-31 2008-12-04 The University Of Western Ontario Biomarker for hypertriglyceridemia
CN101636506A (en) * 2006-08-02 2010-01-27 梅约医学教育与研究基金会 Method for selecting therapeutic agents
CN105018602A (en) * 2015-06-26 2015-11-04 上海市精神卫生中心 Antipsychotic drug related metabolism syndrome susceptible gene and application thereof
WO2019104146A1 (en) * 2017-11-22 2019-05-31 Mayo Foundation For Medical Education And Research Methods and materials for assessing and treating obesity
CN111118150A (en) * 2020-03-02 2020-05-08 上海百傲科技股份有限公司 Method, kit, primer pair and probe for detecting IL28B gene

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101636506A (en) * 2006-08-02 2010-01-27 梅约医学教育与研究基金会 Method for selecting therapeutic agents
WO2008144940A1 (en) * 2007-05-31 2008-12-04 The University Of Western Ontario Biomarker for hypertriglyceridemia
CN105018602A (en) * 2015-06-26 2015-11-04 上海市精神卫生中心 Antipsychotic drug related metabolism syndrome susceptible gene and application thereof
WO2019104146A1 (en) * 2017-11-22 2019-05-31 Mayo Foundation For Medical Education And Research Methods and materials for assessing and treating obesity
CN111118150A (en) * 2020-03-02 2020-05-08 上海百傲科技股份有限公司 Method, kit, primer pair and probe for detecting IL28B gene

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
A J RISSELADA等: "Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study", 《THE PHARMACOGENOMICS JOURNAL》 *
AURÉLIEDELACRÉTAZ等: "Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs", 《GENE》 *
HIROSHI UJIKE等: "Multiple Genetic Factors in Olanzapine-Induced Weight Gain in Schizophrenia Patients: A Cohort Study", 《JOURNAL OF CLINICAL PSYCHIATRY》 *
JEE-YOUNGLEE等: "Genetic variant of HTR2A associates with risk of impulse control and repetitive behaviors in Parkinson’s disease", 《PARKINSONISM & RELATED DISORDERS》 *
R C SMITH等: "Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia", 《THE PHARMACOGENOMICS JOURNAL》 *
STEFAN F.C.VAESSEN等: "Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study", 《JOURNAL OF LIPID RESEARCH》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2810798C1 (en) * 2022-10-14 2023-12-28 Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр психиатрии и неврологии имени В.М. Бехтерева" (ФГБУ "НМИЦ ПН им. В.М. Бехтерева" Минздрава России) Method of selecting treatment tactics for patients with antipsychotic-induced extrapyramidal disorders

Similar Documents

Publication Publication Date Title
CN101892302B (en) Application and detection kit of rs2336384 locus of hypertension susceptibility gene
CN102586408B (en) The detection method of hypertension susceptible gene Mfn2 mononucleotide polymorphism site rs3820189 and detection kit
Rosmond et al. Polymorphisms of the β2‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men
CN101892311A (en) Detection method and detection kit for single nucleotide polymorphism site rs7550536 of hypertension susceptibility gene
Dong et al. T594M and G442V polymorphisms of the sodium channel β subunit and hypertension in a black population
Elouej et al. Association of rs9939609 polymorphism with metabolic parameters and FTO risk haplotype among Tunisian metabolic syndrome
CN110699440A (en) Primer and method for detecting SNP (single nucleotide polymorphism) locus of gene related to metformin personalized medicine
Pinto et al. Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia
CN107893114A (en) For primer pair, kit and the method for instructing fentanyl class medicine personalized medicine related gene to detect
CN113584147A (en) Gene polymorphism detection kit for guiding medication of psychosis
Li et al. Potential diagnostic markers of diabetic retinopathy: serum LncRNA MIAT, HOTTIP, SNHG16
Irvin et al. CPT1A: the future of heart disease detection and personalized medicine?
CN110295225A (en) Primer combination and kit and method for instructing Lovastatin drug personalized medicine related gene to detect
Mick et al. Genome-wide association study of blood pressure response to methylphenidate treatment of attention-deficit/hyperactivity disorder
CN105018602B (en) Susceptibility gene of antipsychotic drug-related metabolic syndrome and application thereof
CN111662977A (en) Gene probe, chip and kit for detecting metabolic influence of anti-psychotropic drugs and application of gene probe, chip and kit
Cheng et al. N-acetyltransferase 2 genetic polymorphisms and anti-tuberculosis-drug-induced liver injury: a correlation study
CN101886129B (en) Method for detecting mononucleotide polymorphism locus rs388915 of hypertension susceptibility genes AGTR 1 and detection kit
CN101886121B (en) Detection method and detection kit for rs873457 site of hypertension susceptibility gene
Olivi et al. PEAR1 is not a human hypertension-susceptibility gene
CN112695083B (en) Nucleic acid composition and kit for detecting gene polymorphism of medicine for hypertension
CN110157798B (en) Primer probe combination for guiding polymorphism of gene locus of diabetes personalized medicine, application and kit thereof
CN120843668A (en) A dynamic assessment system for the risk of abnormal glucose and lipid metabolism based on SNP and gene analysis and its application in neuropsychiatric drug treatment
CN101892298B (en) Detection method and kit for hypertension susceptibility gene single nucleotide polymorphism site rs2236055
CN113373211A (en) Related gene detection kit for guiding anxiety disorder medication and application

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination