Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of Chinese Academy of Sciences, Shanghai, China.
J Hypertens. 2011 Jan;29(1):70-5. doi: 10.1097/HJH.0b013e32833f60ab.
Recent genome-wide association studies have identified a number of variants influencing blood pressure. We aimed to examine whether these associations can be replicated in Chinese.
We genotyped eight of these variants (in or near FGF5, CYP17A1, MTHFR, ZNF652, PLCD3, ATP2B1, c10orf107) in a population-based cohort of Chinese Hans (N = 3210). Logistics regression and generalized linear analyses were applied to test for association of each variant with hypertension risk and blood pressure (BP), BMI, waistline and high-sensitivity C-reactive protein (hsCRP), respectively.
Six variants showed directionally consistent association with blood pressure and risk of hypertension, of which four (FGF5, two in CYP17A1, MTHFR) reached significance. The associations were most pronounced for FGF5-rs16998073 [SBP: β = 1.97 mmHg/allele, P = 0.0006; DBP: β = 0.95 mmHg/allele, P = 0.0008, hypertension: odds ratio (OR) 1.36/allele, P = 0.0001]. Effect size of FGF5-rs16998073 on SBP and hypertension were significantly more pronounced in Han Chinese compared to white Europeans. None of these variants was associated with BMI, waistline or hsCRP that are the well established risk factors for hypertension. The genetic risk score, calculated as the sum of BP-increasing alleles of FGF5-rs16998073, CYP17A1-rs11191548, CYP17A1-rs1004467 and MTHFR-rs17367504, was significantly associated with increased SBP (1.16 mmHg/allele, P = 9.01E-5), DBP (0.51 mmHg/allele, P = 4.40E-4) and hypertension risk (OR = 1.22/allele, P = 2.74E-7).
Variants in or near FGF5, CYP17A1 and MTHFR contributed to variation in BP and hypertension risk. Effect sizes of these three loci tended to be larger in Chinese than in white Europeans, but more studies with larger sample size are required for a definitive conclusion.
最近的全基因组关联研究已经确定了一些影响血压的变异。我们旨在检验这些关联是否可以在中国人群中得到复制。
我们对中国汉族人群（N=3210）的一个基于人群的队列中进行了 8 个变体（位于或接近 FGF5、CYP17A1、MTHFR、ZNF652、PLCD3、ATP2B1、c10orf107 内或附近）的基因分型。应用逻辑回归和广义线性分析分别检验每个变体与高血压风险和血压（BP）、BMI、腰围和高敏 C 反应蛋白（hsCRP）的关联。
六个变体与血压和高血压风险呈方向一致的关联，其中四个（FGF5、CYP17A1 中的两个、MTHFR）达到显著水平。FGF5-rs16998073 的关联最为明显[SBP：β=1.97mmHg/等位基因，P=0.0006；DBP：β=0.95mmHg/等位基因，P=0.0008，高血压：比值比（OR）1.36/等位基因，P=0.0001]。与白人欧洲人相比，FGF5-rs16998073 对 SBP 和高血压的遗传效应在汉族人群中更为明显。这些变体均与 BMI、腰围或 hsCRP 无关，后者是高血压的公认危险因素。FGF5-rs16998073 的 BP 升高等位基因的总和计算出的遗传风险评分与 SBP（1.16mmHg/等位基因，P=9.01E-5）、DBP（0.51mmHg/等位基因，P=4.40E-4）和高血压风险（OR=1.22/等位基因，P=2.74E-7）显著相关。
FGF5、CYP17A1 和 MTHFR 中的变体导致 BP 和高血压风险的变异。这些三个位点的遗传效应大小在中国人群中似乎大于白人欧洲人，但需要更大样本量的研究来得出明确的结论。
