CN116287190B - Polymorphic site combination, kit and detection system for evaluating curative effect of ARB drugs - Google Patents
Polymorphic site combination, kit and detection system for evaluating curative effect of ARB drugs Download PDFInfo
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Abstract
The invention discloses a polymorphic locus combination for evaluating the curative effect of ARB drugs, which comprises the following steps: the rs6749447 locus, the rs10737062 locus, the rs10752271 locus and the rs3814995 locus for evaluating the efficacy of losartan; the rs1367117 site for evaluating the efficacy of losartan; the rs5443 locus, the rs1983023 locus and the rs2008584 locus are used for evaluating the curative effect of telmisartan; polymorphic site rs1275988 for assessing candesartan efficacy. A kit for evaluating the curative effect of ARB drugs comprises a primer group for identifying polymorphic sites. A detection system for evaluating the curative effect of ARB drugs. The invention has the beneficial effects of early identifying the benefited crowd using a specific ARB drug and effectively reducing the blood pressure of the patient.
Description
Technical Field
The present invention relates to the fields of medicine and biotechnology. More particularly, the invention relates to a polymorphic site combination, a kit and a detection system for evaluating the curative effect of ARB drugs.
Background
Hypertension is one of the most common cardiovascular diseases in the world, often causes complications of organs such as heart, brain, kidney and the like, and seriously endangers human health. According to the research data of nutrition and health conditions of residents nationwide in 2019, the prevalence of hypertension of adults in China is 18.8%, and about 1.6 million of patients with hypertension are nationwide. China has become one of the most people suffering from hypertension. Because the standard reaching rate of the treatment of the hypertension is low, multiple dangerous factors are often combined, and a huge progress space still exists in the aspects of the management and the medication of the hypertension. Common antihypertensive drugs include five classes: 1. calcium channel blockers (calcium channel blockers, CCB); 2. angiotensin converting enzyme antagonists (ACEI, actein-converting enzyme inhibitor); 3. angiotensin ii receptor Antagonists (ARBs); 4. diuretics; 5. beta blockers.
Among them, angiotensin ii (Ang ii) receptor Antagonists (ARB) inhibit the conversion of Ang i to Ang ii, specifically antagonize Angiotensin converting enzyme 1 receptor (AT 1), antagonize AT1 by 8500 times higher than AT2, inhibit vasoconstriction and release of aldosterone by selectively blocking the binding of Ang ii to AT1 receptor, and produce a hypotensive effect. Common drugs are losartan, irbesartan, candesartan and telmisartan. The four drugs of losartan, irbesartan, candesartan and telmisartan relate to polymorphic sites of a plurality of genes, and the efficacy, metabolism or absorption of different drugs by different types of different genes are different, namely the curative effects of drug treatment are different among different individuals.
The gene efficacy scoring (genetic efficacy score, GES) is a drug efficacy evaluation system for establishing expected benefits of an individual using a certain drug based on gene polymorphism, and how to use GES to make model prediction on an individual level is an effective method for identifying people who may benefit from using a certain specific ARB drug, so as to identify potential beneficiary people early, select ARB drugs with better efficacy for treatment, effectively reduce blood pressure of patients, suppress medical cost increase, and prolong expected life of people.
Disclosure of Invention
It is an object of the present invention to solve at least the above problems and to provide at least the advantages to be described later.
It is still another object of the present invention to provide a polymorphic site combination for assessing the efficacy of an ARB-type drug, and a kit for assessing the efficacy of an ARB-type drug, comprising a primer set for identifying each polymorphic site in said polymorphic site combination. Further provides a detection system for evaluating the curative effect of the ARB drugs, which comprises a kit, and can early identify the beneficiary population using a specific ARB drug and effectively reduce the blood pressure of patients.
To achieve these objects and other advantages and in accordance with the purpose of the invention, there is provided a polymorphic site combination for evaluating the efficacy of ARB-type drugs, comprising:
polymorphic sites for assessing the efficacy of losartan, including the site rs6749447, the site rs10737062, the site rs10752271, the site rs 3814995;
a polymorphic site for assessing irbesartan efficacy comprising the site rs 1367117;
polymorphic sites for assessing telmisartan efficacy, including an rs5443 site, an rs1983023 site, an rs2008584 site;
a polymorphic site for assessing candesartan efficacy comprising a site of rs 1275988.
A kit for assessing the efficacy of an ARB-type drug comprising primer sets 1-9 for identifying each polymorphic site in said combination of polymorphic sites, wherein:
primer group 1 for identifying rs6749447 locus consists of nucleotide sequences shown in SEQ ID No.1 and SEQ ID No. 2;
primer group 2 for identifying the locus rs10737062 consists of nucleotide sequences shown in SEQ ID No.3 and SEQ ID No. 4;
primer group 3 for identifying the locus rs10752271 consists of nucleotide sequences shown in SEQ ID No.5 and SEQ ID No. 6;
primer group 4 for identifying the locus rs3814995 consists of nucleotide sequences shown in SEQ ID No.7 and SEQ ID No. 8;
primer group 5 for identifying rs1367117 locus consists of nucleotide sequences shown in SEQ ID No.9 and SEQ ID No. 10;
primer group 6 for identifying rs5443 locus consists of nucleotide sequences shown in SEQ ID No.11 and SEQ ID No. 12;
primer group 7 for identifying the locus rs1983023 consists of nucleotide sequences shown in SEQ ID No.13 and SEQ ID No. 14;
primer group 8 for identifying the locus rs2008584 consists of nucleotide sequences shown in SEQ ID No.15 and SEQ ID No. 16;
primer group 9 for identifying the locus rs1275988 consists of nucleotide sequences shown as SEQ ID No.17 and SEQ ID No. 18.
A test system for assessing the efficacy of an ARB drug comprising:
the kit is used for detecting genotypes of individuals to be detected carrying polymorphic loci;
a storage unit for storing the weight w of each polymorphic site and the genotype scores m of different genotypes of each polymorphic site;
a curative effect score determining unit connected with the detecting unit and the storage unit and used for determining the genotype score M of each polymorphic site of the individual to be detected according to the detected genotype, determining the curative effect score M of the individual to be detected for each drug according to the weight w of the polymorphic site and the genotype score M of the detected polymorphic site,wherein n is the number of polymorphic loci corresponding to the ARB drugs, and w n Weighting the nth polymorphic site corresponding to the ARB medicine, m n The genotype of the ARB drug at the corresponding n-th polymorphic site was scored.
Preferably, each polymorphic site weight w is:
the weight of the rs6749447 locus is 0.85; the weight of the rs10737062 locus is 1.07;
the weight of the rs10752271 locus is 1.07; the weight of the rs3814995 locus is 0.93;
the weight of the rs1367117 locus is 0.78; the weight of the rs5443 locus is 0.98;
the weight of the rs1983023 locus is 0.98; the weight of the rs2008584 locus is 1.00;
the weight at the rs1275988 site is 0.95.
Preferably, the different genotypes of each polymorphic site are classified as good, bad and/or fast and slow in terms of drug effect according to the study content in the literature, and based thereon a corresponding genotype score m is given for each genotype, in particular:
the risk allele at position rs6749447 is G, m=0 when genotypes GG and GT, and m=1 when genotype TT;
the risk allele at position rs10737062 is a, m=0 when genotype is AA, and m=1 when genotype is AG and GG;
the risk allele at position rs10752271 is a, m=0 when genotype is AA, and m=1 when genotype is AG and GG;
the risk allele at position rs3814995 is C, m=0 when genotypes are CC and CT, and m=1 when genotype is TT;
the risk allele at position rs1367117 is a, m=0 when genotype is AA, and m=1 when genotype is AG and GG;
the risk allele at the rs5443 locus is T, m=0 when genotype is TT, m=1 when genotype is CC and CT;
the risk allele at position rs1983023 is C, m=0 when genotype is TC and CC, and m=1 when genotype is TT;
the risk allele at position rs2008584 is a, m=0 when genotypes AG and GG, and m=1 when genotype AA;
the risk allele at position rs1275988 is T, m=0 when genotype is TT, and m=1 when genotype is CC and CT.
Preferably, the test sample of the test subject is one of blood, urine, saliva, gastric juice, hair or biopsy of the test subject.
The invention at least comprises the following beneficial effects:
the method can simultaneously detect gene polymorphism of sites related to curative effects of four ARB drugs aiming at hypertensive patients, and give scores for comprehensively guiding the administration of the ARB drugs, thereby realizing accurate administration, effectively reducing the blood pressure of the patients and reducing adverse reactions of the drugs.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Detailed Description
The present invention is described in further detail below with reference to examples to enable those skilled in the art to practice the same by referring to the description.
1. Obtaining 9 polymorphic sites (SNP sites) related to the drug effect (effect) and metabolic rate (Metabolism/PK) of an angiotensin II receptor Antagonist (ARB) therapeutic drug through literature and data mining, namely obtaining a polymorphic site combination for evaluating the ARB therapeutic drug effect, comprising:
polymorphic sites for assessing the efficacy of losartan, including the site rs6749447, the site rs10737062, the site rs10752271, the site rs 3814995;
a polymorphic site for assessing irbesartan efficacy comprising the site rs 1367117;
polymorphic sites for assessing telmisartan efficacy, including an rs5443 site, an rs1983023 site, an rs2008584 site;
a polymorphic site for assessing candesartan efficacy comprising a site of rs 1275988.
2. Designing a corresponding primer sequence based on the polymorphic site combinations, wherein in one specific embodiment, the primer set for evaluating the therapeutic effect of the angiotensin II receptor antagonist type drug comprises:
primer group 1 for detecting gene polymorphism of rs6749447 locus of STK39 gene, and comprising nucleotide sequences shown in SEQ ID No.1 and SEQ ID No. 2;
amplification of the upstream primer: GTTTCACTTACGCCCAAGCT (SEQ ID No. 1);
amplifying the downstream primer: TGCAGTTAGGTCACCTCCTT (SEQ ID No. 2);
primer group 2 for detecting gene polymorphism of rs10737062 locus of CAMK1D gene, composed of nucleotide sequences shown in SEQ ID No.3 and SEQ ID No. 4;
amplification of the upstream primer: GCTGGCTGAAACTGGCCTAA (SEQ ID No. 3);
amplifying the downstream primer: CTTTCCCAACTGCCCCCAAC (SEQ ID No. 4);
primer group 3 for detecting gene polymorphism of rs10752271 locus of CAMK1D gene, composed of nucleotide sequences shown in SEQ ID No.5 and SEQ ID No. 6;
amplification of the upstream primer: CTGGTGGAATACCATGGAGCT (SEQ ID No. 5);
amplifying the downstream primer: TCTGGATTCCATGCAGCGTT (SEQ ID No. 6);
primer group 4 for detecting gene polymorphism of rs3814995 locus of NPHS1 gene, which consists of nucleotide sequences shown in SEQ ID No.7 and SEQ ID No. 8;
amplification of the upstream primer: GGGCTTGAAGCCCAGACTCA (SEQ ID No. 7);
amplifying the downstream primer: CTCCCCCTGCAGGTGAATTC (SEQ ID No. 8);
primer group 5 for detecting gene polymorphism of rs1367117 locus of APOB gene, and comprising nucleotide sequences shown in SEQ ID No.9 and SEQ ID No. 10;
amplification of the upstream primer: AGTCACATCCGTGCCTGGTG (SEQ ID No. 9);
amplifying the downstream primer: AACCCAGGAGGCATGTTGAT (SEQ ID No. 10);
primer group 6 for detecting gene polymorphism of rs5443 locus of GNB3 gene, and comprising nucleotide sequences shown in SEQ ID No.11 and SEQ ID No. 12;
amplification of the upstream primer: CCCAGGTCTGATCCCTGACC (SEQ ID No. 11);
amplifying the downstream primer: CAGTGACAAGGGACAGCAGT (SEQ ID No. 12);
primer group 7 for detecting gene polymorphism of rs1983023 locus of UGT1A3 gene, and comprising nucleotide sequences shown in SEQ ID No.13 and SEQ ID No. 14;
amplification of the upstream primer: GGTGCTGGATTGACTTGGAGA (SEQ ID No. 13);
amplifying the downstream primer: TGGAGGCTGGCTATGTGGTT (SEQ ID No. 14);
primer group 8 for detecting gene polymorphism of rs2008584 locus of UGT1A3 gene, and comprising nucleotide sequences shown in SEQ ID No.15 and SEQ ID No. 16;
amplification of the upstream primer: CCCAGTCCCTTGGTGAGCAG (SEQ ID No. 15);
amplifying the downstream primer: GCACACATGGGCAAGACAACC (SEQ ID No. 16);
primer group 9 for detecting gene polymorphism of rs1275988 locus of KCNK3 gene, and comprising nucleotide sequences shown in SEQ ID No.17 and SEQ ID No. 18;
amplification of the upstream primer: CTGGCTGACTGCCTCCTGAG (SEQ ID No. 17);
amplifying the downstream primer: CCCAGCAGAACCGGGATCTA (SEQ ID No. 18);
the primer group has the advantages of accurate quality, high sensitivity and strong specificity.
3. A kit for assessing the efficacy of an angiotensin II receptor antagonist comprising:
10 to 100pmol of each primer contained in the primer set 1 to 9, and other reagents known in the art, such as:
50. Mu.L of 10 Xamplification buffer;
200. Mu. Mol/L each of the 4 dNTP mixtures;
template DNA 0.1-2 mug;
TaqDNA polymerase 2.5u;
Mg 2+ 1.5mmol/L。
4. a system for detecting the efficacy of an angiotensin II receptor Antagonist (ARB) therapeutic class of drugs comprising: the method comprises the following steps:
(1) the kit is used for detecting genotypes of the polymorphic loci carried by the individuals to be detected, and the detection of the genotypes of the polymorphic loci carried by the individuals to be detected comprises the following steps:
1) Obtaining a sample to be detected of an individual to be detected, extracting sample DNA to be detected through the sample to be detected, wherein the specific sample to be detected of the individual to be detected is one of blood, urine, saliva, gastric juice, hair or biopsy of the individual to be detected, taking blood of the individual to be detected as an example:
obtaining peripheral blood of an individual to be tested to obtain a sample to be tested;
extracting DNA of a subject from a sample to be tested to obtain sample DNA;
2) Carrying out PCR amplification and purification on sample DNA;
2.1, uniformly mixing the PCR reaction liquid, adding sample DNA to form a reaction system, and carrying out PCR amplification according to a PCR reaction program to obtain a PCR amplification product, wherein the PCR reaction program is as follows: 94 ℃/4min;90-95 ℃/20s,50-60 ℃/30s,70-75 ℃/60s,45 cycles; maintaining at 72deg.C for 5min; keeping the temperature at 4 ℃ until the reaction is finished;
2.2, purifying the PCR amplification product by using an agarose gel electrophoresis method to obtain a purified PCR amplification product;
3) Sequencing the purified PCR amplified product
3.1, carrying out sequencing PCR amplification reaction on the purified PCR amplification product to obtain a sequencing product, wherein:
the reaction system for the sequencing PCR amplification reaction is shown in the following table:
and (3) configuring a reaction system: in a 96-well reaction plate, adding water, centrifuging at 1000rpm to the bottom of the 96-well reaction plate after the water is added, adding 2 mu L of sequencing primer, centrifuging at 1000rpm to the bottom of the 96-well reaction plate after the water is added, adding purified PCR amplification product, centrifuging at 1000rpm to the bottom of the 96-well reaction plate after the water is added, and adding 4ul of diluted Big Dye, wherein the sequencing primer is an amplification upstream primer corresponding to each polymorphic site;
after the addition, a sealing film is stuck on a reaction plate, the reaction plate is pressed, and the reaction plate is put into a PCR instrument, wherein the reaction parameters are set as follows: 96 ℃ for 12s,50 ℃ for 6s and 60 ℃ for 3min, 24 cycles are total; preserving heat at 10 ℃;
3.2, purifying the sequencing product to obtain a purified sequencing product, wherein the purification comprises the following steps:
taking down the 96-well reaction plate, instantly centrifuging to 1200rpm on a centrifuge, adding Stop Solution 1.5 mu L into the centrifuged 96-well reaction plate hole, and instantly centrifuging to 1200rpm on the centrifuge;
adding 100 mu L of 75% isopropanol into a 96-well reaction plate, shaking and uniformly mixing, and standing at room temperature for about 10 minutes in a dark place; after balancing, centrifuging for 30min at 4000rpm and 20 ℃;
reversely buckling the STOP key according to the centrifugal machine when the instant centrifugal machine is started to 800rpm on the water absorbing paper;
adding 100 mu L of 75% isopropanol without shaking and uniformly mixing; after trimming, the mixture was centrifuged at 4000rpm at 20℃for 10min.
And (3) reversely buckling, instantly centrifuging on absorbent paper to 800rpm, and blowing by an electric fan for about 10 minutes in a light-proof environment according to the STOP key of the centrifuge to remove residual isopropanol.
Add 10. Mu.L Hi-Di solution to each well (10. Mu.L Hi-Di solution to the wells) in the reaction plate, mix well by shaking, then spin to 1000rpm instantaneously;
3.3, placing the processed 96 Kong Fanying plate in a plastic frame of an upper machine, covering a rubber pad, checking whether 96 holes are aligned, and sequencing on the upper machine to obtain genotypes of polymorphic sites carried by individuals to be detected;
(2) a storage unit for storing the weight w of each polymorphic site and the genotype scores m of different genotypes of each polymorphic site, specifically:
i, weight w of each polymorphic site is shown in Table 1 below:
TABLE 1 polymorphic site weights (weight)
II, classifying different genotypes according to research contents in literature: the drug was effective, poor and metabolic rate fast, slow, and gave the corresponding genotype scores m for each genotype, as shown in table 2 below:
TABLE 2 genotyping of polymorphic loci
(3) Efficacy scoringA determining unit connected with the detecting unit and the storage unit and used for determining the genotype scores M of the polymorphic sites of the individuals to be detected according to the detected genotypes, determining the curative effect scores M of the individuals to be detected for the medicines according to the weight w of the polymorphic sites and the genotype scores M of the detected polymorphic sites,wherein n is the number of polymorphic loci corresponding to the ARB drugs, and w n Weighting the nth polymorphic site corresponding to the ARB medicine, m n Genotype scores measured for the nth polymorphic site corresponding to this ARB class of drug, specifically:
for a efficacy score M of losartan,wherein m is 1 Genotype scores measured for the corresponding rs6749447 locus of losartan; m is m 2 Genotype scores measured for the corresponding rs10737062 locus of losartan; m is m 3 Genotype scores measured for the corresponding rs10752271 locus of losartan; m is m 4 Genotype scores measured for the corresponding rs3814995 locus of losartan;
efficacy score for irbesartan, M, m=0.78×m 1 Wherein m is 1 Genotype scores measured for the corresponding rs1367117 locus of irbesartan;
for a efficacy score of telmisartan M,wherein m is 1 Genotype scores measured for the rs5443 locus corresponding to telmisartan; m is m 2 Genotype scores measured for positions rs1983023 corresponding to telmisartan; m is m 3 Genotype scores measured for positions rs2008584 corresponding to telmisartan;
efficacy score M for candesartan, m=0.95×m 1 Wherein m is 1 Genotype scores measured for the rs1275988 locus corresponding to candesartan;
4) And determining the ARB drugs with optimal curative effect scores as recommended drugs.
5. Guiding effect of medication
Example 1
The number ZR00080 of the testers, the female sex, 59 years old, and the ethnic group Chinese had the history of hypertension, diabetes and helicobacter pylori infection. The patient is treated before the blood pressure is controlled poorly. The nifedipine controlled release tablet is taken at 30mg qd to control the blood pressure, has side effects of leg swelling, and has the current systolic pressure (SBP) of 140-150mmHg and the diastolic pressure (DBP) of 80-90mmHg. Other oral medications include metformin and pioglitazone to control blood glucose, atorvastatin to control blood lipid, aspirin and folic acid to prevent platelets.
The primer set and/or the kit are used for gene detection of the patient, and the detection results are shown in the following table:
detection result:
calculated, losartan score was 0, irbesartan score was 0.78, telmisartan score was 0.99, and candesartan score was 0.95.
According to the gene detection result, the efficacy of telmisartan is predicted to be better through pharmacodynamic analysis, so that the treatment scheme is modified to be 80mg qd of telmisartan. After 1 month, the patients can check before, the self-complaint blood pressure SBP is 110-120mmHg, the DBP is 70-80mmHg, and the blood pressure control condition is good.
Example 2
The number ZR00089 of the testers is equal to the number ZR00089, the female sex is 81 years old, the ethnic group Chinese has 20 years old of hypertension, diabetes and lithangiuria, and no drug allergy history exists. Father and sister in family history all suffer from hypertension. The patient is treated before the blood pressure is controlled poorly. The felodipine sustained release tablet is taken 5mg qd (taken in the afternoon) and telmisartan 40mg qd (taken in the morning) to control blood pressure, and the current Systolic Blood Pressure (SBP) of blood pressure is 180mmHg and the Diastolic Blood Pressure (DBP) of blood pressure is 60mmHg. Other oral medications include atorvastatin to control blood lipid and pulse-activating drinks.
The primer set and/or the kit are used for gene detection of the patient, and the detection results are shown in the following table:
detection result:
the losartan score was calculated to be 0.48, the irbesartan score was calculated to be 0.78, the telmisartan score was calculated to be 0.66, and the candesartan score was calculated to be 0.95.
According to the gene detection result, the efficacy of the candesartan is best, the irbesartan is inferior, the telmisartan and the losartan are inferior, but the treatment scheme is modified to be 150mg qd of the irbesartan, and the oral administration is carried out at 3-4 pm, and 5mg qd of the felodipine sustained release tablet is additionally carried out in the morning because of the lack of the candesartan in hospitals. Patients were reviewed before 1 month later, and the complaint blood pressure SBP was 115-135mmHg and DBP was 45-50mmHg. The blood pressure control condition is good.
Although embodiments of the present invention have been disclosed above, it is not limited to the details and embodiments shown, it is well suited to various fields of use, and further modifications may be readily made by those skilled in the art without departing from the general concepts defined by the claims and the equivalents thereof, and therefore the invention is not limited to the specific details and examples shown and described herein.
Claims (3)
1. A kit for evaluating the curative effect of ARB drugs is characterized by comprising a primer group 1-9 for identifying each polymorphic site in a polymorphic site combination for evaluating the curative effect of ARB drugs,
the polymorphic site combinations for evaluating the curative effect of the ARB drugs are as follows:
polymorphic sites for assessing losartan efficacy, which are the rs6749447 site, the rs10737062 site, the rs10752271 site and the rs3814995 site;
a polymorphic site for assessing irbesartan efficacy, which is the rs1367117 site;
polymorphic sites for assessing telmisartan efficacy, which are the rs5443 site, the rs1983023 site and the rs2008584 site;
a polymorphic site for assessing candesartan efficacy, which is the rs1275988 site;
wherein:
primer group 1 for identifying rs6749447 locus consists of nucleotide sequences shown in SEQ ID No.1 and SEQ ID No. 2;
primer group 2 for identifying the locus rs10737062 consists of nucleotide sequences shown in SEQ ID No.3 and SEQ ID No. 4;
primer group 3 for identifying the locus rs10752271 consists of nucleotide sequences shown in SEQ ID No.5 and SEQ ID No. 6;
primer group 4 for identifying the locus rs3814995 consists of nucleotide sequences shown in SEQ ID No.7 and SEQ ID No. 8;
primer group 5 for identifying rs1367117 locus consists of nucleotide sequences shown in SEQ ID No.9 and SEQ ID No. 10;
primer group 6 for identifying rs5443 locus consists of nucleotide sequences shown in SEQ ID No.11 and SEQ ID No. 12;
primer group 7 for identifying the locus rs1983023 consists of nucleotide sequences shown in SEQ ID No.13 and SEQ ID No. 14;
primer group 8 for identifying the locus rs2008584 consists of nucleotide sequences shown in SEQ ID No.15 and SEQ ID No. 16;
primer group 9 for identifying the locus rs1275988 consists of nucleotide sequences shown as SEQ ID No.17 and SEQ ID No. 18.
2. A test system for assessing the efficacy of an ARB-type drug comprising:
the kit according to claim 1, for detecting genotypes of individuals to be detected carrying the polymorphic sites;
a storage unit for storing the weight w of each polymorphic site and the genotype scores m of different genotypes of each polymorphic site;
a curative effect score determining unit connected with the detecting unit and the storage unit and used for determining the genotype score M of each polymorphic site of the individual to be detected according to the detected genotype, and determining the curative effect score M, M=of the individual to be detected for each drug according to the weight w of the polymorphic site and the genotype score M of the detected polymorphic siteWherein n is the number of polymorphic loci corresponding to the ARB drugs, and w n Weighting the nth polymorphic site corresponding to the ARB medicine, m n Genotype scores for the nth polymorphic site corresponding to the ARB class of drug;
the weights w of the polymorphic sites are respectively as follows:
the weight of the rs6749447 locus is 0.85; the weight of the rs10737062 locus is 1.07; the weight of the rs10752271 locus is 1.07; the weight of the rs3814995 locus is 0.93; the weight of the rs1367117 locus is 0.78; the weight of the rs5443 locus is 0.98; the weight of the rs1983023 locus is 0.98; the weight of the rs2008584 locus is 1.00; the weight of the rs1275988 locus is 0.95;
according to the research content in the literature, different genotypes of each polymorphic site are classified into good drug effect, poor drug effect and/or rapid and slow metabolic rate, and corresponding genotype scores m are given for each genotype based on the different genotypes, specifically:
the risk allele at position rs6749447 is G, m=0 when genotypes GG and GT, and m=1 when genotype TT;
the risk allele at position rs10737062 is a, m=0 when genotype is AA, and m=1 when genotype is AG and GG;
the risk allele at position rs10752271 is a, m=0 when genotype is AA, and m=1 when genotype is AG and GG;
the risk allele at position rs3814995 is C, m=0 when genotypes are CC and CT, and m=1 when genotype is TT;
the risk allele at position rs1367117 is a, m=0 when genotype is AA, and m=1 when genotype is AG and GG;
the risk allele at the rs5443 locus is T, m=0 when genotype is TT, m=1 when genotype is CC and CT;
the risk allele at position rs1983023 is C, m=0 when genotype is TC and CC, and m=1 when genotype is TT;
the risk allele at position rs2008584 is a, m=0 when genotypes AG and GG, and m=1 when genotype AA;
the risk allele at position rs1275988 is T, m=0 when genotype is TT, and m=1 when genotype is CC and CT.
3. The test system for assessing the efficacy of an ARB drug according to claim 2 wherein the test sample of the test individual is one of blood, urine, saliva, gastric juice, hair or biopsy of the test individual.
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| CN101063166A (en) * | 2006-04-30 | 2007-10-31 | 安徽省生物医学研究所 | Reagent case for predicting action effect of angiotensin conversion enzyme inhibitor medicament |
| CN111197076A (en) * | 2018-11-19 | 2020-05-26 | 北京毅新博创生物科技有限公司 | Antihypertensive drug irbesartan medication guidance and gene detection kit |
| CN111206083A (en) * | 2018-11-21 | 2020-05-29 | 北京毅新博创生物科技有限公司 | Detection kit for medication guidance gene of telmisartan medicament for reducing hypertension |
| CN112080563A (en) * | 2020-09-01 | 2020-12-15 | 美思睿(北京)生物科技有限公司 | Kit for detecting accurate medication genes of chronic diseases |
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| CN101063166A (en) * | 2006-04-30 | 2007-10-31 | 安徽省生物医学研究所 | Reagent case for predicting action effect of angiotensin conversion enzyme inhibitor medicament |
| CN111197076A (en) * | 2018-11-19 | 2020-05-26 | 北京毅新博创生物科技有限公司 | Antihypertensive drug irbesartan medication guidance and gene detection kit |
| CN111206083A (en) * | 2018-11-21 | 2020-05-29 | 北京毅新博创生物科技有限公司 | Detection kit for medication guidance gene of telmisartan medicament for reducing hypertension |
| CN112080563A (en) * | 2020-09-01 | 2020-12-15 | 美思睿(北京)生物科技有限公司 | Kit for detecting accurate medication genes of chronic diseases |
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