Han Xikun, Hu Zunsong, Chen Jing, Huang Jianfeng, Huang Chen, Liu Fangchao, Gu Charles, Yang Xueli, Hixson James E, Lu Xiangfeng, Wang Laiyuan, Liu De-Pei, He Jiang, Chen Shufeng, Gu Dongfeng
Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Los Angeles, USA.
Am J Hypertens. 2017 Apr 1;30(4):427-434. doi: 10.1093/ajh/hpw200.
The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population.
We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag single-nucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses.
Systolic BP (SBP) response to high-sodium intervention significantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10-4). SBP responses (95% confidence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was significantly associated with SBP response to high-sodium intervention (P = 1.00 × 10-6) and diastolic BP response to low-sodium intervention (P = 9.80 × 10-4).
These findings suggested that genetic variants of NADPH oxidase-related genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these findings is warranted.
本研究旨在全面测试烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶相关基因的遗传变异与中国人群饮食钠干预血压（BP）反应之间的关联。
我们在中国农村的1906名参与者中进行了为期7天的低钠干预，随后进行了为期7天的高钠干预。使用随机零血压计在基线和每次饮食干预时测量血压。线性混合效应模型用于评估11个NADPH氧化酶相关基因中63个标签单核苷酸多态性与饮食钠干预血压反应的加性关联。使用截短产物法进行基于基因的分析。在所有分析中使用Bonferroni方法调整多重检验。
收缩压（SBP）对高钠干预的反应随着RAC1中标记rs6967221的次要T等位基因数量的增加而显著降低（P = 4.51×10-4）。在高钠干预期间，基因型CC、CT和TT的SBP反应（95%置信区间）分别为5.03（4.71, 5.36）、4.20（3.54, 4.85）和0.56（-1.08, 2.20）mmHg。基于基因的分析显示，RAC1与高钠干预的SBP反应（P = 1.00×10-6）和低钠干预的舒张压反应（P = 9.80×10-4）显著相关。
这些发现表明，NADPH氧化酶相关基因的遗传变异可能导致中国人群钠干预血压反应的差异。这些发现值得进一步重复验证。
