AUTHOR=Wei Bi-Liu , Yin Rui-Xing , Liu Chun-Xiao , Deng Guo-Xiong , Guan Yao-Zong , Zheng Peng-Fei 

TITLE=CYP17A1–ATP2B1 SNPs and Gene–Gene and Gene–Environment Interactions on Essential Hypertension

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.720884

DOI=10.3389/fcvm.2021.720884

ISSN=2297-055X

ABSTRACT=<p><bold>Background:</bold> The association between the <italic>CYP17A1</italic> and <italic>ATP2B1</italic> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> The frequencies of minor alleles and genotypes of four SNPs were different between the two groups (<italic>p</italic> &lt; 0.001). According to genetic dominance model analysis, three (rs1004467, rs11191548, and rs17249754) SNPs and two haplotypes (<italic>CYP17A1</italic> rs1004467G-rs11191548C and <italic>ATP2B1</italic> rs1401982G-rs17249754A) were negatively correlated, whereas rs1401982 SNP and the other two haplotypes (<italic>CYP17A1</italic> rs1004467A-rs11191548T and <italic>ATP2B1</italic> rs1401982A-rs17249754G) were positively associated with hypertension risk (<italic>p</italic> ≤ 0.002 for all). Two best significant two-locus models were screened out by GMDR software involving SNP–environment (rs11191548 and BMI ≥ 24 kg/m<sup>2</sup>) and haplotype–environment (<italic>CYP17A1</italic> rs1004467G-rs11191548C and BMI ≥ 24 kg/m<sup>2</sup>) interactions (<italic>p</italic> ≤ 0.01). The subjects carrying some genotypes increased the hypertension risk.</p><p><bold>Conclusions:</bold> Our outcomes implied that the rs1004467, rs11191548, and rs17249754 SNPs and <italic>CYP17A1</italic> rs1004467G-rs11191548C and <italic>ATP2B1</italic> rs1401982G-rs17249754A haplotypes have protective effects, whereas the rs1401982 SNP and <italic>CYP17A1</italic> rs1004467A-rs11191548T and <italic>ATP2B1</italic> rs1401982A-rs17249754G haplotypes showed adverse effect on the prevalence of hypertension. Several SNP–environment interactions were also detected.</p>