Abstract
Background: The association between the CYP17A1 and ATP2B1 SNPs and essential hypertension (referred to as hypertension) is far from being consistent. In addition to the heterogeneity of hypertension resulting in inconsistent results, gene–gene and gene–environment interactions may play a major role in the pathogenesis of hypertension rather than a single gene or environmental factor.Methods: A case–control study consisting of 1,652 individuals (hypertension, 816; control, 836) was conducted in Maonan ethnic minority of China. Genotyping of the four SNPs was performed by the next-generation sequencing technology.Results: The frequencies of minor alleles and genotypes of four SNPs were different between the two groups (p < 0.001). According to genetic dominance model analysis, three (rs1004467, rs11191548, and rs17249754) SNPs and two haplotypes (CYP17A1 rs1004467G-rs11191548C and ATP2B1 rs1401982G-rs17249754A) were negatively correlated, whereas rs1401982 SNP and the other two haplotypes (CYP17A1 rs1004467A-rs11191548T and ATP2B1 rs1401982A-rs17249754G) were positively associated with hypertension risk (p ≤ 0.002 for all). Two best significant two-locus models were screened out by GMDR software involving SNP–environment (rs11191548 and BMI ≥ 24 kg/m2) and haplotype–environment (CYP17A1 rs1004467G-rs11191548C and BMI ≥ 24 kg/m2) interactions (p ≤ 0.01). The subjects carrying some genotypes increased the hypertension risk.Conclusions: Our outcomes implied that the rs1004467, rs11191548, and rs17249754 SNPs and CYP17A1 rs1004467G-rs11191548C and ATP2B1 rs1401982G-rs17249754A haplotypes have protective effects, whereas the rs1401982 SNP and CYP17A1 rs1004467A-rs11191548T and ATP2B1 rs1401982A-rs17249754G haplotypes showed adverse effect on the prevalence of hypertension. Several SNP–environment interactions were also detected.
Highlights
Essential hypertension is a regular multifactorial disease affecting about one-fourth of adults worldwide [1]
The rs1401982 single-nucleotide polymorphism (SNP) enhanced the risk of hypertension, whereas the rs1004467, rs11191548, and rs17249754 SNPs decreased the susceptibility of hypertension in the dominant model (p ≤ 0.002 for all)
When the SNP–environment interaction was analyzed, we found that the individuals with rs11191548 TC/CC genotypes and body mass index (BMI) ≥ 24 kg/m2 raised the risk of hypertension compared to the individuals with rs11191548 TT and BMI ≥ 24 kg/m2
Summary
Essential hypertension (referred to as hypertension) is a regular multifactorial disease affecting about one-fourth of adults worldwide [1]. Most of its potential mechanisms are still unknown It is well-known that environmental factors, including excessive salt intake, tobacco use, physical inactivity, alcohol abuse, overweight, and obesity, increase blood pressure (BP) levels [2], but about half of population BP changes are determined by genetic factors [3, 4]. Genome-wide association studies (GWASs) can screen and analyze hypertension risk genes [5]. Two large GWASs (Global BPgen and CHARGE) have identified 14 risk loci that reached genome-wide significant closely related to BP in 2009, including ATPase, Ca2+ transporting, plasma membrane 1 gene (ATP2B1) and cytochrome P450, family 17, subfamily A, and polypeptide 1 gene (CYP17A1) [6, 7]. The association between the CYP17A1 and ATP2B1 SNPs and essential hypertension (referred to as hypertension) is far from being consistent. In addition to the heterogeneity of hypertension resulting in inconsistent results, gene–gene and gene–environment interactions may play a major role in the pathogenesis of hypertension rather than a single gene or environmental factor
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
