Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in she ethnic minority of China

• Published in: Atherosclerosis 2011-12, Vol.219 (2), p.709-714
• Main Authors: Lin, Yinghua, Lai, Xiaolan, Chen, Bin, Xu, Yuan, Huang, Baoying, Chen, Zichun, Zhu, Shaoheng, Yao, Jin, Jiang, Qiqin, Huang, Huibin, Wen, Junping, Chen, Gang
• Format: Article
• Language: English
• Subjects: Adult; adults; alleles; Analysis of Variance; Asian Continental Ancestry Group - genetics; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Blood Pressure - genetics; body mass index; Calcium Channels, L-Type - genetics; Cardiology. Vascular system; Cardiovascular; Carrier Proteins - genetics; Case-Control Studies; Chi-Square Distribution; China - epidemiology; confidence interval; Coronary heart disease; cross-sectional studies; cumulative risk; Europeans; Female; females; Gene Frequency; Genetic Predisposition to Disease; genetic variation; Heart; Humans; Hypertension; Hypertension - enzymology; Hypertension - ethnology; Hypertension - genetics; Hypertension - physiopathology; Linear Models; loci; Logistic Models; logit analysis; Male; males; Medical sciences; Middle Aged; minorities (people); Minority Groups; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Prehypertension; Prehypertension - enzymology; Prehypertension - ethnology; Prehypertension - genetics; Prehypertension - physiopathology; Risk Assessment; Risk Factors; single nucleotide polymorphism; Single nucleotide polymorphism (SNP); Steroid 17-alpha-Hydroxylase - genetics
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2011.09.006

Abstract Objectives Two large-scale genome-wide association studies (GWAs) have identified multiple variants associated with blood pressure (BP) or hypertension. The present study was to investigate whether some variations were associated with BP traits and hypertension or even prehypertension in adult She ethnic minority of China. Methods The population of the present study comprised 4460 (1979 males and 2481 females, respectively) unrelated she ethnic minority based on a cross-sectional study from Ningde City in Fujian province of China. There were 1692 hypertensives, 1600 prehypertensives and 1168 normotensive controls, respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3-TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses were performed in an additive genetic model. Results As the minor allele of rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6 loci, linear regression analyses revealed that rs11191548 in CYP17A1 and rs11014166 in CACNB2 were significantly associated with systolic BP ( β = −1.17, P = 0.002 and β = −0.50, P = 0.006, respectively), while only SNP rs11191548 was significantly associated with diastolic BP ( β = −0.56, P = 0.002) after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found to be significantly related to hypertension (odds ratios [OR] and (95% confidence interval [CI]): 0.79 (0.65–0.97) and 1.19 (1.01–1.41), respectively) in logistic regression analyses after adjusted by age, sex and BMI. In addition, we found that combined risk alleles of the 6 SNPs increased risk of hypertension in a stepwise fashion ( P for trend < 0.001). However, none of the 6 SNPs was significantly associated with BMI or prehypertension status. While logistic analysis showed that subjects with cumulative risk alleles more than 9 had significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001) compared with those with risk alleles less than 4. Conclusions We replicated that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or hypertension in She population. In addition, although we failed to observe single gene associated with prehypertension, we first found that conjoint effect of multiple risk alleles on BP might increase the risk of progressing to prehypertension.