Association of CYP17A1 Genetic Polymorphisms and Susceptibility to Essential Hypertension in the Southwest Han Chinese Population

Abstract

BackgroundThe CYP17A1 gene encodes for cytochrome P450 enzyme CYP17A1, which is involved with the steroidogenic pathway including mineralocorticoids. The CYP17A1 polymorphisms might affect enzyme activity, then leading to a state of mineralocorticoid 11-deoxycorticosterone excess characterized by hypertension, suppressed plasma renin activity, and low aldosterone concentrations. The aim of this study was to investigate the contribution of CYP17A1 polymorphisms in inducing the susceptibility to essential hypertension among the Southwest Han Chinese population.Material/MethodsEight single nucleotide polymorphisms of CYP17A1 were genotyped in a case-control study for samples by polymerase chain reaction-restriction fragment length polymorphism analysis.ResultsThe polymorphisms rs11191548 and rs4919687 were significantly associated with hypertension risk, which was confirmed by systolic and diastolic blood pressure distribution analyses between different genotype groups, and these two polymorphisms were found in linkage disequilibrium. The rs4919687 polymorphism was estimated to cause the destruction of exonic splicing silencer (ESR and Motif 3) sites and to transform the transcription factor AREB6 binding site, respectively, in the bioinformatics analyses. The haplotypes rs4919686A-rs3740397G -rs4919687C-rs743572C-rs11191548C and rs4919686A-rs3740397G-rs4919687T-rs743572C- rs11191548T were found to be susceptible to essential hypertension.ConclusionsOur findings suggest that the CYP17A1 polymorphisms could be a genetic risk factor for essential hypertension among the Yunnan Han Chinese population, which would have implications for the treatment of this complex disorder.

The CYP17A1 gene polymorphisms are associated with hypercholesterolemia in Han Chinese

“…The CYP17A1 gene encodes the cytochrome P450 enzyme CYP17A1 , which is responsible for the synthesis of steroid hormones. In several previous studies, the CYP17A1 polymorphisms rs1004467 and rs11191548 were associated with hypertension or BP levels. The rs1004467 G‐allele was a protective factor for hypertension in some studies of the Han Shanghai and Japanese populations, which was similar to the findings of the present study.…”

“…The rs1004467 G‐allele was significantly associated with a reduced risk for hypercholesterolemia and the lower serum TC levels in the present study. However, in several studies completed in Japanese and Yunnan, Xinjiang Han populations, there were no insignificant associations between rs1004467 and hypertension or BP levels . In a study including 3503 Chinese children aged 6–18 years, the rs1004467 G‐allele was associated with BMI .…”

“…However, in several studies completed in Japanese and Yunnan, Xinjiang Han populations, there were no insignificant associations between rs1004467 and hypertension or BP levels. 18,20,21 In a study including 3503 Chinese children aged 6-18 years, the rs1004467 G-allele was associated with BMI. 22 The inconsistency can be attributed to the different genetic backgrounds, age structure, living habits and environmental factors.…”

“…The rs11191548 minor C-allele was associated with reduced hypertension risk or BP levels in several studies performed the European and Asian populations. 4,[16][17][18][19][20]23 The SNP rs11191548 near CYP17A1 was associated with HDL-C and leptin in a study including a total of 3503 children from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. 24 These results of these studies were similar to those of the present study.…”

Analysis of putative cis-regulatory elements regulating blood pressure variation

“…Additionally, as the CYP17A1 gene primarily demonstrates an adrenal effect in the monogenic disorder [44], we also examined the associations of these three variants in the GTEx portal with adrenal gland expression data for both genes; all have p > 0.26 for CYP17A1 and p > 0.04 for C10orf32 . This may reflect an endothelial-cell-specific effect for C10orf32 rather than a tissue-type effect, especially as this locus has been identified in several previous BP GWAS studies, [40,43,45–47]; it may also not be very informative for the kidney, though suitable expression data for kidney would be required to assess this.…”