Li Jin, Shi Jinxiu, Huang Wei, Sun Jielin, Wu Ying, Duan Qing, Luo Jingchun, Lange Leslie A, Gordon-Larsen Penny, Zheng S Lilly, Yuan Wentao, Wang Ying, Popkin Barry M, Mo Zengnan, Xu Jianfeng, Du Shufa, Mohlke Karen L, Lange Ethan M
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Curriculum in Bioinformatics & Computational Biology, University of North Carolina, Chapel Hill, North Carolina, USA;
Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China;
Am J Hypertens. 2015 Aug;28(8):1031-7. doi: 10.1093/ajh/hpu263. Epub 2015 Jan 23.
The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI).
We used a linear mixed-effects model to test for variant main effects and variant interactions with age, sex, and BMI on systolic (SBP) and diastolic (DBP) blood pressure in 7,319 Chinese adults from the China Health and Nutrition Survey (CHNS). We attempted to replicate our significant interaction findings in 1,996 Chinese men from the Fangchenggang Area Male Health and Examination Survey (FAMHES).
Two variants (rs11105378 near ATP2B1 and rs1458038 near FGF5) were significantly associated (P < 0.00625 = 0.05/8) with both SBP and DBP in CHNS. Variant rs1378942 near CSK was nominally associated with SBP (P = 0.01). The signal at rs1458038 exhibited a genotype-by-BMI interaction affecting blood pressure (P interaction = 0.0018 for SBP; P interaction = 0.049 for DBP), with the strongest variant effects in those with the highest BMI. In FAMHES, rs1458038 also showed stronger effects on SBP and DBP among men with the highest BMI.
Our findings suggest high BMI increases the effect of the blood pressure-increasing allele at rs1458038 near FGF5, further highlighting the importance of obesity prevention in reducing hypertension risk.
本研究的目的是调查4个候选变异与血压的遗传关联，并测试年龄、性别和体重指数（BMI）等环境因素的修饰作用。
我们使用线性混合效应模型，对来自中国健康与营养调查（CHNS）的7319名中国成年人中，各变异对收缩压（SBP）和舒张压（DBP）的主效应以及变异与年龄、性别和BMI的相互作用进行检验。我们试图在中国防城港地区男性健康与体检调查（FAMHES）的1996名中国男性中重复我们的显著相互作用结果。
在CHNS中，两个变异（ATP2B1附近的rs11105378和FGF5附近的rs1458038）与SBP和DBP均显著相关（P < 0.00625 = 0.05/8）。CSK附近的变异rs1378942与SBP名义上相关（P = 0.01）。rs1458038处的信号表现出基因型与BMI的相互作用，影响血压（SBP的P相互作用 = 0.0018；DBP的P相互作用 = 0.049），在BMI最高的人群中变异效应最强。在FAMHES中，rs1458038在BMI最高的男性中对SBP和DBP也表现出更强的效应。
我们的研究结果表明，高BMI增加了FGF5附近rs1458038处升高血压等位基因的效应，进一步凸显了预防肥胖在降低高血压风险中的重要性。
