CN117089612A - A method of applying enalapril to reduce blood pressure based on genotyping results - Google Patents

Abstract

The present invention provides a method for accurately applying enalapril to reduce blood pressure based on genotyping results, which includes the following steps: selecting relevant gene sites by querying the PharmGKB database; combined analysis of NR3C2 gene loci rs5522, BDKRB2 gene loci rs1799722 and rs12050217, SLCO1B1 gene locus rs4149056, CES1 gene locus rs71647871, compare the effects of each genotype of each gene locus on the antihypertensive effect, risk of cough adverse reactions, and metabolic clearance rate in the body, and formulate a precise application strategy for enalapril. The present invention classifies hypertensive patients through combined analysis of genotypes of gene sites related to enalapril, and adopts corresponding selection strategies in terms of whether to use enalapril and initial usage and dosage, thereby improving the efficiency of enalapril. Treatment efficiency improves medication compliance and quality of life of patients with hypertension.

Description

A method of applying enalapril to reduce blood pressure based on genotyping results

Technical field

The present invention relates to the technical field of molecular biology detection, in particular, to the technical field of genetic detection; specifically, to a method for accurately applying enalapril to reduce blood pressure based on genotyping results.

Background technique

SNPs have two significant characteristics: first, they are large in number. A large number of SNPs facilitates the selection of appropriate sites for disease research, and also makes the vast majority of genomic regions covered by SNPs; the other characteristic is that most SNP sites are Dimorphism, that is, there are only two expression forms (genotypes) at one locus, so it is easy to design high-throughput automated detection methods. It is precisely because of these two characteristics that SNP sites are increasingly favored by researchers and are known as the successor to restriction fragment length polymorphism (RFLP) and short tandem repeats (STR). ), the third generation of molecular markers. Before and after the completion of the Human Genome Project, the focus of genomics research gradually shifted to the field of SNPs. Therefore, SNPs have been used in genetic markers, biological population genetics, biological taxonomy, genetics and breeding, species or human evolution, legal science, pharmacogenomics, etc. It has important applications in various fields.

Cardiovascular disease is the leading disease burden on human health worldwide. The prevalence of cardiovascular disease in my country continues to rise. Hypertension is one of the most common cardiovascular diseases and a major risk factor for cardiovascular disease. Epidemiological studies show that blood pressure levels are linearly related to the incidence of cardiovascular disease; elevated blood pressure is an independent risk factor for stroke and coronary heart disease. Hypertension is the main cause of life-threatening cardiovascular and cerebrovascular diseases such as myocardial infarction, stroke, and renal insufficiency. Therefore, effective control of blood pressure has great clinical significance in preventing the occurrence of cardiovascular and cerebrovascular complications in patients with hypertension.

Pharmacogenomics has become an important tool to guide clinical medication and assess the risk of serious adverse drug reactions. By detecting drug metabolizing enzymes and drug target genes, clinicians can be guided to select appropriate antihypertensive drugs and dosages for specific patients, thereby improving the effectiveness and safety of antihypertensive drug treatment. Every aspect of how a drug works may show significant differential responses due to genetic variation. Differences in drug effects manifest themselves as differences in pharmacokinetics and pharmacodynamics.

Chinese patent application "Kit for predicting the effects of angiotensin-converting enzyme inhibitor drugs" (Patent No.: 200610011839.0) discloses a method that utilizes proline carboxypeptidase (PRCP), an important enzyme in the vascular and endothelial function regulation pathways. ) gene's single nucleotide polymorphism site E112D genotype and the effect of angiotensin-converting enzyme inhibitor drugs to predict the effect of drugs containing angiotensin-converting enzyme inhibitors. The kit contains polymorphism typing oligonucleotides used to detect the E112D polymorphic site genotype of the PRCP gene in biological samples, as well as related reagents. It can guide doctors to implement predictive medication, select according to individual differences, and improve It has confirmed the effectiveness and safety of clinical medication, and provided a basis for the development of new drugs that act on PRCP to treat hypertension. However, the above-mentioned invention needs to judge the rationality of medication based on the blood pressure-lowering effect and other toxic and side effects produced by patients with different genotypes after taking the medication for a period of time. It takes a long time in clinical application, and the prediction results are affected by various factors of patients. Physiological parameters (such as gender, age, BMI, smoking, drinking, and baseline homocysteine) have a greater impact.

As the closest existing technology, the Chinese patent application "Uses, methods and kits for predicting the effect of angiotensin-converting enzyme inhibitor drugs by polymorphic site genotype" (Patent No.: 200510130528.1) involves homocysteine The polymorphic site genotype of the key enzyme gene in the amino acid metabolism pathway is used to predict the effect of angiotensin-converting enzyme inhibitor (ACEI) drugs and is used to determine the homocysteine metabolism pathway. Polymorphism typing oligonucleotides for key enzyme gene polymorphism site genotypes. By measuring the polymorphism site genotypes of key enzyme genes on the homocysteine metabolism pathway, we can predict patients containing ACEI drugs. Effective methods and kits. However, the detection methods and kits provided by this invention patent only target the polymorphic sites of key enzyme genes in the homocysteine metabolism pathway. The detection objects have limitations, and the operation is cumbersome, making it difficult to meet the needs of rapid and accurate clinical use. needs.

Therefore, there is a need for a kit and its supporting detection method that can quickly and effectively detect the polymorphic sites of all genes related to target drug metabolism, improve the efficiency of drug use, and reduce the incidence of adverse reactions. It is beneficial to clinical development of more reasonable and effective medication regimens.

Contents of the invention

In view of this, the purpose of the present invention is to provide a method for accurately applying enalapril to reduce blood pressure based on genotyping results. By detecting the genotype of the SNP site of the patient's enalapril-related drug gene, the genotypes of each site are combined. Analyze, determine the benefits and risks of patients using enalapril, and select appropriate initial usage and dosage for patients, providing a fast, effective, and safe antihypertensive program for patients with hypertension.

The present invention provides a method for accurately applying enalapril to reduce blood pressure based on genotyping results, which includes the following steps:

S1. By querying the PharmGKB database, select relevant gene sites that have a great impact on the effects of enalapril;

The genetic loci that have a great influence on the effect of enalapril include:

The NR3C2 gene locus rs5522 has a high mutation rate in Asian populations and has a great impact on the antihypertensive effect of enalapril;

The BDKRB2 gene loci rs1799722 and rs12050217, and the SLCO1B1 gene locus rs4149056, which have a great impact on the risk of cough caused by enalapril;

CES1 gene locus rs71647871, which has a great influence on the metabolic clearance rate of enalapril;

S2. Combined analysis of the genotypes of each gene locus selected in step S1, and compare the effects of each genotype of each gene locus on the antihypertensive effect, the risk of cough adverse reactions, and the metabolic clearance rate in the body;

Analyze the antihypertensive effect obtained by using enalapril in patients with TT, CC and CT genotypes of the NR3C2 gene locus rs5522;

Analyze patients with CC, CT and TT genotypes at the BDKRB2 gene locus rs1799722, patients with GG, AG and AA genotypes at rs12050217, and patients with TT, CT and CC at the SLCO1B1 gene locus rs4149056 who developed poor cough after using enalapril risk of reaction;

Analyze the in vivo metabolic clearance rate of enalapril in patients with CT, TT and CC genotypes of the CES1 gene locus rs71647871;

S3. Based on the degree of influence of each genotype of the gene locus on the antihypertensive efficacy of enalapril, the risk of cough adverse reactions and the metabolic clearance rate, formulate a precise application strategy for enalapril.

Further, the method of formulating a precise application strategy for enalapril in step S3 includes the following steps:

S31. Before using antihypertensive drugs in patients with hypertension, detect the genotypes of five loci: NR3C2 rs5522, BDKRB2 rs1799722 and rs12050217, SLCO1B1 rs4149056, and CES1 rs71647871;

S32. Based on the patient's genotype results, decide whether to use enalapril and the initial dosage of enalapril.

Further, the method of detecting the genotypes of five loci in step S31 includes:

Design the primer sequence of the detection site as follows:

rs5522-f2 TTGGGCTGTGCACTGGAAAACT

rs5522-r2 GTTTGTGTGAACACGCCCTTGAG

rs1799722-f2 CAGAGCGGAGAGCGAAGGTGG

rs1799722-r2 GCTCATCTTTCAAGGGCTGGCTA

rs12050217-f2 GTAGCACTGTAACCACC

rs12050217-r2 CTAACATCTGTTAGATGG

rs4149056-f2 TACTATGGGAGTCTCCCCTATT

rs4149056-r2 TTGTTTAAAGGAATCTGGGTCAT

rs71647871-f2 ACGTTGGATGATCATAGGTTGATGCCGCAC

rs71647871-r2 ACGTTGGATGTATGTTGCTTCCTCTCTGCC.

Further, the method of determining whether to use enalapril and the initial usage and dosage of enalapril in step S32 includes:

S321, based on the test results of NR3C2 gene locus rs5522, which is related to the antihypertensive effect of enalapril, and the test results of BDKRB2 gene locus rs1799722 and rs12050217, which are related to the risk of cough adverse reactions of enalapril, and SLCO1B1 gene locus rs4149056 , determine whether to give the patient enalapril for antihypertensive treatment;

S322. Determine the initial usage and dosage of enalapril based on the detection results of CES1 gene locus rs71647871, which is related to the metabolic clearance rate of enalapril.

Further, the method of determining whether to administer enalapril to the patient for antihypertensive treatment in step S321 includes:

When the test results of gene loci related to the antihypertensive effect of enalapril indicate that the patient has poor efficacy in antihypertensive treatment with enalapril, or there are three gene loci associated with the risk of cough adverse reactions of enalapril. When the test results of two or more sites indicate a high risk of cough (see Table 1), the patient will not be treated with enalapril for antihypertensive treatment;

When the test results of gene loci related to the antihypertensive effect of enalapril indicate that the patient's antihypertensive treatment with enalapril is effective, and only one of the three gene loci associated with the risk of cough adverse reactions of enalapril When the test results of one or no sites indicate a high risk of cough (see Table 1), the patient is given antihypertensive treatment with enalapril.

Further, the method for determining the initial usage and dosage of enalapril in step S322 includes:

When the test results of gene loci related to the metabolic clearance rate of enalapril indicate rapid metabolism, the initial dosage of enalapril is 10 mg each time, twice a day;

When the test results of gene loci related to the metabolic clearance rate of enalapril indicate slow metabolism, the initial dosage of enalapril is 10 mg once a day.

See Table 2:

Further, the analysis results of the genotype of each gene locus selected by the combined analysis of step S2 include:

Patients with TT genotype of NR3C2 gene locus rs5522 can obtain greater antihypertensive effect than patients with CC and CT genotypes after taking enalapril;

Patients with the CC genotype of the BDKRB2 gene locus rs1799722 have a lower risk of cough adverse reactions than patients with the CT and TT genotypes after taking enalapril; patients with the GG and AG genotypes of the BDKRB2 gene locus rs12050217 have a lower risk of developing cough adverse reactions than those with the CT and TT genotypes. Patients with the AA genotype have a lower risk of developing cough adverse reactions; patients with the TT genotype of the SLCO1B1 gene locus rs4149056 have a lower risk of developing cough adverse reactions after taking enalapril than patients with the CT and CC genotypes;

The metabolic clearance rate of enalapril in patients with CT and TT genotypes of CES1 gene locus rs71647871 is lower than that in patients with CC genotype.

The embodiment research of the present invention shows that compared with the traditional decision of whether to use enalapril and its dosage regimen based on doctor's experience, the precise strategy of determining the dosage regimen of enalapril through the combination of enalapril-related genotypes can Significantly improves the success rate of enalapril in the treatment of hypertension. The blood pressure compliance rate of hypertensive patients treated with enalapril through a precise strategy is as high as 97.44%, which is much higher than the 84.14% of patients treated with enalapril through a traditional dosing strategy. The precise dosing strategy can also significantly shorten the time for hypertension to reach the target. The average time for hypertensive patients treated with enalapril to reach the target through the precise strategy is 11.31 days, which is much shorter than the 16.27 days for patients treated with the traditional dosing strategy.

The precise dosing strategy of the present invention can also significantly improve the quality of life of patients. The median health self-score of hypertensive patients treated with enalapril through the precise strategy is 85 points, which is much higher than the 80 points for patients treated with the traditional dosing strategy. . The precision dosing strategy can also significantly improve patients' medication compliance. The median Morisky medication compliance score of hypertensive patients treated with enalapril through the precision strategy is 7.62, which is much higher than the 6.25 score for patients using the traditional dosing strategy. .

Compared with the prior art, the beneficial effects of the present invention are:

The present invention performs combined analysis on the genotypes of SNP sites of genes related to enalapril, classifies different types of hypertensive patients, and adopts similar methods in terms of whether to use enalapril and the initial usage and dosage of enalapril. The corresponding selection strategy provides direction guidance for the treatment of hypertension, can improve the rate of achieving the target of hypertension treatment, shorten the time to achieve the target of blood pressure, and increase the efficiency of treatment of hypertension; and, the present invention detects the genotype of the SNP site of the enalapril-related gene Results: Classification of hypertensive patients can provide precise guidance on whether individual patients are suitable for enalapril treatment and the required dosage, improve the efficiency of enalapril treatment, and improve the medication compliance and quality of life of hypertensive patients.

Detailed ways

Exemplary embodiments will be described in detail herein. The implementations described in the following exemplary embodiments do not represent all implementations consistent with the present disclosure. Rather, they are merely examples of devices and products consistent with aspects of the disclosure as detailed in the appended claims.

The terminology used in this disclosure is for the purpose of describing particular embodiments only and is not intended to be limiting of the disclosure. As used in this disclosure and the appended claims, the singular forms "a," "the" and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. It will also be understood that the term "and/or" as used herein refers to and includes any and all possible combinations of one or more of the associated listed items.

It should be understood that although the terms first, second, third, etc. may be used in this disclosure to describe various information, the information should not be limited to these terms. These terms are only used to distinguish information of the same type from each other. For example, without departing from the scope of the present disclosure, the first information may also be called second information, and similarly, the second information may also be called first information. Depending on the context, the word "if" as used herein may be interpreted as "when" or "when" or "in response to determining."

The embodiments of the present invention will be described in further detail below.

Embodiments of the present invention provide a method for accurately applying enalapril to reduce blood pressure based on genotyping results, which includes the following steps:

S1. By querying the PharmGKB database, select relevant gene sites that have a great impact on the effects of enalapril;

The genetic loci that have a great influence on the effect of enalapril include:

The NR3C2 gene locus rs5522 has a high mutation rate in Asian populations and has a great impact on the antihypertensive effect of enalapril;

The BDKRB2 gene loci rs1799722 and rs12050217, and the SLCO1B1 gene locus rs4149056, which have a great impact on the risk of cough caused by enalapril;

CES1 gene locus rs71647871, which has a great influence on the metabolic clearance rate of enalapril;

S2. Combined analysis of the genotypes of each gene locus selected in step S1, and compare the effects of each genotype of each gene locus on the antihypertensive effect, the risk of cough adverse reactions, and the metabolic clearance rate in the body;

Analyze the antihypertensive effect obtained by using enalapril in patients with TT, CC and CT genotypes of the NR3C2 gene locus rs5522;

Analyze patients with CC, CT and TT genotypes at the BDKRB2 gene locus rs1799722, patients with GG, AG and AA genotypes at rs12050217, and patients with TT, CT and CC at the SLCO1B1 gene locus rs4149056 who developed poor cough after using enalapril risk of reaction;

Analyze the in vivo metabolic clearance rate of enalapril in patients with CT, TT and CC genotypes of the CES1 gene locus rs71647871;

The analysis results of the genotypes of each gene locus selected in step S1 of the combined analysis include:

Patients with TT genotype of NR3C2 gene locus rs5522 can obtain greater antihypertensive effect than patients with CC and CT genotypes after taking enalapril;

Patients with the CC genotype of the BDKRB2 gene locus rs1799722 have a lower risk of cough adverse reactions than patients with the CT and TT genotypes after taking enalapril; patients with the GG and AG genotypes of the BDKRB2 gene locus rs12050217 have a lower risk of developing cough adverse reactions than those with the CT and TT genotypes. Patients with the AA genotype have a lower risk of developing cough adverse reactions; patients with the TT genotype of the SLCO1B1 gene locus rs4149056 have a lower risk of developing cough adverse reactions after taking enalapril than patients with the CT and CC genotypes;

The metabolic clearance rate of enalapril in patients with CT and TT genotypes of CES1 gene locus rs71647871 is lower than that in patients with CC genotype.

S3. Based on the degree of influence of each genotype of the gene locus on the antihypertensive efficacy of enalapril, the risk of cough adverse reactions and the metabolic clearance rate, formulate a precise application strategy for enalapril.

The method of formulating a precise application strategy for enalapril includes the following steps:

S31. Before using antihypertensive drugs in patients with hypertension, detect the genotypes of five loci: NR3C2 rs5522, BDKRB2 rs1799722 and rs12050217, SLCO1B1 rs4149056, and CES1 rs71647871;

Methods for detecting genotypes at five loci include:

Design the primer sequence of the detection site as follows:

rs5522-f2 TTGGGCTGTGCACTGGAAAACT

rs5522-r2 GTTTGTGTGAACACGCCCTTGAG

rs1799722-f2 CAGAGCGGAGAGCGAAGGTGG

rs1799722-r2 GCTCATCTTTCAAGGGCTGGCTA

rs12050217-f2 GTAGCACTGTAACCACC

rs12050217-r2 CTAACATCTGTTAGATGG

rs4149056-f2 TACTATGGGAGTCTCCCCTATT

rs4149056-r2 TTGTTTAAAGGAATCTGGGTCAT

rs71647871-f2 ACGTTGGATGATCATAGGTTGATGCCGCAC

rs71647871-r2 ACGTTGGATGTATGTTGCTTCCTCTCTGCC.

S32. Based on the patient's genotype results, decide whether to use enalapril and the initial dosage of enalapril.

The method for determining whether to use enalapril and the initial usage and dosage of enalapril includes:

S321, based on the test results of NR3C2 gene locus rs5522, which is related to the antihypertensive effect of enalapril, and the test results of BDKRB2 gene locus rs1799722 and rs12050217, which are related to the risk of cough adverse reactions of enalapril, and SLCO1B1 gene locus rs4149056 , determine whether to give the patient enalapril for antihypertensive treatment;

The method for determining whether to administer enalapril to the patient for antihypertensive treatment includes:

When the test results of gene loci related to the antihypertensive effect of enalapril indicate that the patient has poor efficacy in antihypertensive treatment with enalapril, or there are three gene loci associated with the risk of cough adverse reactions of enalapril. When the test results of two or more sites indicate a high risk of cough (see Table 1), the patient will not be treated with enalapril for antihypertensive treatment;

When the test results of gene loci related to the antihypertensive effect of enalapril indicate that the patient's antihypertensive treatment with enalapril is effective, and only one of the three gene loci associated with the risk of cough adverse reactions of enalapril When the test results of one or no sites indicate a high risk of cough (see Table 1), the patient is given antihypertensive treatment with enalapril.

S322. Determine the initial usage and dosage of enalapril based on the detection results of CES1 gene locus rs71647871, which is related to the metabolic clearance rate of enalapril.

The method for determining the initial usage and dosage of enalapril includes:

When the test results of gene loci related to the metabolic clearance rate of enalapril indicate rapid metabolism, the initial dosage of enalapril is 10 mg each time, twice a day;

When the test results of gene loci related to the metabolic clearance rate of enalapril indicate slow metabolism, the initial dosage of enalapril is 10 mg once a day.

See Table 2.

Research on the embodiments of the present invention shows that compared with the traditional decision of whether to use enalapril and its dosage regimen based on doctor's experience, the precise strategy of determining the dosage regimen of enalapril through the combination of enalapril-related genotypes can significantly improve To determine the success rate of enalapril in treating hypertension, we randomly divided 222 hypertensive patients whose blood pressure did not reach the standard into two groups. One group used the present invention to determine whether the patient should apply enalapril and its initial administration based on the genotyping results. The other group decided on the dosage based on doctors’ experience and reviewed it once a week to evaluate the blood pressure, quality of life and medication compliance of the two groups of patients. The advantages and disadvantages of the two methods were compared based on the review results in the fourth week. Research shows that compared with the traditional decision of whether to use enalapril and its dosage regimen based on doctors' experience, the blood pressure compliance rate of hypertensive patients treated with enalapril through a precise strategy is as high as 97.44%, which is much higher than that through traditional drug administration. 84.14% of strategy patients. The precise dosing strategy can significantly shorten the time for hypertension to reach the target. The average time for hypertensive patients treated with enalapril to reach the target blood pressure through the precise strategy is 11.31 days, which is much shorter than the 16.27 days for patients treated with the traditional dosing strategy.

The precise dosing strategy of this embodiment can significantly improve the quality of life of patients. The median health self-score of hypertensive patients treated with enalapril through the precise strategy is 85 points, which is much higher than that of patients treated with the traditional dosing strategy. 80 points. The precision dosing strategy can also significantly improve patients' medication compliance. The median Morisky medication compliance score of hypertensive patients treated with enalapril through the precision strategy is 7.62, which is much higher than the 6.25 score for patients using the traditional dosing strategy. .

So far, the technical solution of the present invention has been described in conjunction with the preferred embodiments. However, those skilled in the art can easily understand that the protection scope of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or replacements to relevant technical features, and the technical solutions after these changes or replacements will fall within the protection scope of the present invention.

The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention; for those skilled in the art, the present invention may have various modifications and changes. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention.

Claims (7)

1. The method for precisely applying enalapril to reduce blood pressure based on genotyping results is characterized by comprising the following steps:

s1, selecting related gene loci with great influence on the action of enalapril drugs by inquiring PharmGKB database;

the gene loci with great influence on enalapril effect comprise:

NR3C2 gene locus rs5522 with high mutation rate and great influence on the antihypertensive effect of enalapril in Asian population;

BDKRB2 gene locus rs1799722 and rs12050217 with great influence on cough risk caused by enalapril and SLCO1B1 gene locus rs4149056;

CES1 gene locus rs71647871 which has a large influence on the clearance of metabolism in enalapril;

s2, analyzing genotypes of the gene loci selected in the step S1 in a combined mode, and respectively comparing influences of the genotypes of the gene loci on the antihypertensive effect, the risk of adverse cough reaction and the in-vivo metabolic clearance;

analyzing the antihypertensive effect obtained by using enalapril by TT, CC and CT genotype patients of NR3C2 locus rs5522;

analyzing CC, CT and TT genotype patients of BDKRB2 gene locus rs1799722, GG, AG and AA genotype patients of rs12050217, and risks of adverse cough reactions of TT, CT and CC patients of SLCO1B1 gene locus rs4149056 after enalapril is used;

analyzing the in vivo metabolic clearance of enalapril in CT, TT and CC genotype patients of CES1 locus rs71647871;

s3, based on the influence degree of each genotype of the gene locus on the antihypertensive curative effect, the cough adverse reaction risk and the metabolic clearance of enalapril, a precise application strategy of enalapril is formulated.

2. The method for precisely applying enalapril blood pressure reduction based on genotyping results according to claim 1, wherein the method for preparing the accurate application strategy of enalapril in the step S3 comprises the following steps:

s31, detecting genotypes of five sites of NR3C2 rs5522, BDKRB2 rs1799722 and rs12050217, SLCO1B1 rs4149056 and CES1 rs71647871 before using a antihypertensive drug to a hypertensive patient;

s32, determining whether to use enalapril and the initial usage amount of the enalapril according to the genotype result of the patient.

3. The method for precisely applying enalapril blood pressure reduction based on genotyping results according to claim 2, wherein the method for detecting genotypes of five sites in the step S31 comprises:

the primer sequences of the detection sites were designed as follows:

rs5522-f2 TTGGGCTGTGCACTGGAAAACT

rs5522-r2 GTTGTGTGAACACGCCCTTGAG

rs1799722-f2 CAGAGCGGAGAGCGAAGGTGG

rs1799722-r2 GCTCATCTTTCAAGGGCTGGCTA

rs12050217-f2 GTAGCACTGTAACCACC

rs12050217-r2 CTAACATCTGTTAGATGG

rs4149056-f2 TACTATGGGAGTCTCCCCTATT

rs4149056-r2 TTGTTTAAAGGAATCTGGGTCAT

rs71647871-f2 ACGTTGGATGATCATAGGTTGATGCCGCAC

rs71647871-r2 ACGTTGGATGTATGTTGCTTCCTCTCTGCC 。

4. the method for precisely applying enalapril blood pressure reduction based on genotyping results according to claim 2, wherein the determining whether to use enalapril and the initial usage amount of enalapril in step S32 comprises:

s321, determining whether to subject a patient to pressure reduction treatment by using enalapril according to a NR3C2 gene locus rs5522 detection result related to the pressure reduction effect of enalapril and BDKRB2 gene loci rs1799722 and rs12050217 and SLCO1B1 gene locus rs4149056 detection results related to the cough adverse reaction risk of enalapril;

s322, determining the initial usage amount of enalapril according to the detection result of CES1 gene locus rs71647871 related to the metabolic clearance rate of enalapril.

5. The method for precisely applying enalapril blood pressure reduction based on genotyping results according to claim 4, wherein the determining whether to apply the blood pressure reduction treatment to the patient with enalapril in step S321 comprises:

when the detection result of the gene locus related to the antihypertensive effect of enalapril indicates that the patient has poor curative effect when using the enalapril antihypertensive treatment, or the detection result of two or more loci in the three gene loci related to the adverse reaction risk of the cough of the enalapril indicates that the cough risk is high, the patient is not used for using the enalapril antihypertensive treatment;

when the detection result of the gene locus related to the antihypertensive effect of enalapril indicates that the patient has good curative effect when using the enalapril antihypertensive treatment, or the detection result of only one or no loci among the three gene loci related to the adverse reaction risk of the cough of the enalapril indicates that the cough risk is high, the patient is used for using the enalapril antihypertensive treatment.

6. The method for precisely applying enalapril blood pressure reduction based on genotyping results according to claim 4, wherein the method for determining initial usage amount of enalapril in step S322 comprises:

when the gene locus detection result related to the metabolic clearance of enalapril indicates that metabolism is fast, the initial administration dose of enalapril is 10mg each time, 2 times a day;

when the gene locus detection result related to the metabolic clearance of enalapril suggests slow metabolism, the initial administration dose of enalapril is 10mg each time, 1 time a day.

7. The method for precisely applying enalapril blood pressure reduction based on genotyping results according to claim 1, wherein the analysis result of the genotyping of each gene locus selected in the step S1 by the combination analysis of the step S2 comprises:

the TT genotype patient of NR3C2 locus rs5522 can obtain a greater antihypertensive effect than CC and CT genotype patients after using enalapril;

the risk of cough adverse reaction of CC genotype patients of BDKRB2 locus rs1799722 is lower than that of CT and TT genotype patients after Enalapril is used; patients with GG and AG genotypes at BDKRB2 locus rs12050217 have lower risk of cough adverse reaction than patients with AA genotype after enalapril is used; TT genotype patients with SLCO1B1 locus rs4149056 have lower risk of cough adverse reaction than CT and CC genotype patients after enalapril is used;

CT and TT genotype patients of CES1 locus rs71647871 have lower metabolic clearance of enalapril in vivo than CC genotype patients.