Department of Endocrinology, Ningde Municipal Hospital, Ningde 352100, China.
Atherosclerosis. 2011 Dec;219(2):709-14. doi: 10.1016/j.atherosclerosis.2011.09.006. Epub 2011 Sep 16.
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.
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.
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.
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.
两项大型全基因组关联研究（GWAS）已经确定了多个与血压（BP）或高血压相关的变异。本研究旨在探讨这些变异是否与中国畲族成年人的血压特征和高血压甚至高血压前期有关。
本研究的人群包括来自中国福建省宁德市的 4460 名（男性 1979 名，女性 2481 名）无亲缘关系的畲族人群，采用横断面研究。其中有 1692 名高血压患者、1600 名高血压前期患者和 1168 名血压正常对照者。我们对之前在欧洲人身上进行的 GWAS 报道的 7 个 CYP17A1、PLEKHA7、CACNB2、ATP2B1、TBX3-TBX5、CSK-ULK3 和 SH2B3 中的变异进行了基因分型。所有分析均采用加性遗传模型进行。
由于 SH2B3 中 rs653178 等位基因非常罕见，频率为 0.018，我们在进一步分析中排除了这个单核苷酸多态性（SNP）。在其他 6 个位点中，线性回归分析显示 CYP17A1 中的 rs11191548 和 CACNB2 中的 rs11014166 与收缩压显著相关（β=−1.17，P=0.002 和 β=−0.50，P=0.006），而只有 rs11191548 与舒张压显著相关（β=−0.56，P=0.002），调整年龄、性别和 BMI 后。CACNB2 和 PLEKHA7 中的两个变异被发现与高血压显著相关（logistic 回归分析中的比值比[OR]和 95%置信区间[CI]：0.79（0.65-0.97）和 1.19（1.01-1.41）），调整年龄、性别和 BMI 后。此外，我们发现 6 个 SNP 的复合风险等位基因以渐进的方式增加高血压的风险（趋势 P<0.001）。然而，没有一个 SNP 与 BMI 或高血压前期状态显著相关。虽然逻辑分析显示，累积风险等位基因数大于 9 的患者发生高血压前期的风险显著升高（调整 OR：3.10，P<0.001），与风险等位基因数小于 4 的患者相比。
我们在畲族人群中复制了 CYP17A1、CACNB2 和 PLEKHA7 中的变异与血压特征和/或高血压有关。此外，尽管我们未能观察到与高血压前期相关的单一基因，但我们首次发现，多个风险等位基因的联合效应对血压的影响可能会增加进展为高血压前期的风险。
