Abstract
BackgroundThere is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients.MethodsTotally 2419 Han Chinese hypertensive patients and 126 normotensive controls were recruited in this study. Venous blood samples were collected from each patient, and the genetic polymorphisms of CYP2C9 and AGTR1 were assessed using a gene chip platform. The allele and genotype frequency of each gene and the combined genotypes in this study were analyzed respectively.ResultsThe gene chip analysis identified an allelic frequency of 96.51% for CYP2C9*1 and 3.49% for CYP2C9*3 in the cohort of Han Chinese hypertensive patients. Statistical analysis showed that the frequency of wild-type homozygous for CYP2C9*1/*1 was 93.30%, while the frequency of heterozygous for *1/*3 or mutant homozygous for *3/*3 was 6.41% or 0.29%. Meanwhile, we detected allelic frequencies of 95.06% and 4.94% for the A and C allele of AGTR1, respectively. While the genotype frequency of wild-type homozygous for AA was 90.41%, the frequency of heterozygous for AC or mutant homozygous for CC was 9.30% or 0.29%. Notably, we observed that 84.66% (2048/2419) of the subjects exhibited a combined genotype of CYP2C9 and AGTR1 as *1/*1 + AA, while the combined genotypes *3/*3 + AC or *3/*3 + CC were not detected in hypertension patients. Besides, no significant association was found between normotensive controls and hypertensive patients, or among the three grades of hypertensive patients.ConclusionsThese data revealed the polymorphisms characteristics of CYP2C9 and AGTR1 in Han Chinese hypertensive patients, providing valuable information for genotype-based antihypertension therapy in prospective clinical studies in the future.
Highlights
There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist
The allele and genotype frequencies of Cytochrome P450 2C9 (CYP2C9) and AGTR1 polymorphisms in Han Chinese hypertensive patients The allele frequency and genotype distribution of CYP2C9 or AGRT1 in the hypertensive population were shown in Tables 2 and 3, respectively
In the case of CYP2C9, we found an allelic frequency of 96.51%
Summary
There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients. Hypertension is a complex disease caused by multiple environmental and genetic factors. An effective way to control hypertension is to improve blood pressure management. Hundreds of compounds representing distinct drug classes have been approved for the treatment of hypertension, the control rate of hypertension in Chinese population remains as low as 15.3% [2]. The patients with hypertension have suffered from trial–error switching of drug classes due to interindividual variations that are attributed to genetic and environmental factors [3, 4]
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