Wang Y L, Qi Y, Bai J N, Qi Z M, Li J R, Zhao H Y, Wang Y F, Lu C Z, Xiao Y, Jia N, Wang B, Niu W Q
The Third Division of Cardiology, Department of Internal Medicine, The Second Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, China.
Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
J Hum Hypertens. 2014 Aug;28(8):504-9. doi: 10.1038/jhh.2013.134. Epub 2014 Jan 16.
Converging evidence suggests that the gene encoding solute carrier family 12 member 3 (SLC12A3) is a logical candidate involved in the underlying cause of hypertension. We therefore selected four tag polymorphisms (rs2304483, rs5804, rs8063291 and rs6499857) from SLC12A3 gene to investigate their individual and interactive associations with hypertension in northeastern Han Chinese. There were 1009 hypertensive patients and 756 normotensive controls. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares, and risk estimates were expressed as odds ratio (OR) and 95% confidence interval (95% CI). Overall, there were significant differences in the genotype (P=0.002) and allele (P=0.002) distributions of rs5804 between patients and controls. Compared with the most common haplotype A-C-T-G, haplotype G-C-T-G that was overrepresented in controls (P<0.001) reduced the crude and adjusted risk of hypertension by 36% (OR 0.64; 95% CI 0.50-0.81; P<0.001) and 39% (OR 0.61; 95% CI 0.48-0.79; P<0.001), respectively. Further interaction analyses identified an overall best MDR model including rs5804 and body mass index (P=0.001), which was validated by logistic regression analysis. Taken together, our findings demonstrate a predominant role played by SLC12A3 gene rs5804 in determining hypertension risk among northeastern Han Chinese. Moreover, the interaction of this polymorphism with obesity can enhance risk prediction.
越来越多的证据表明，编码溶质载体家族12成员3（SLC12A3）的基因是参与高血压潜在病因的一个合理候选基因。因此，我们从SLC12A3基因中选择了四个标签单核苷酸多态性（rs2304483、rs5804、rs8063291和rs6499857），以研究它们与中国东北汉族人群高血压的个体及交互关联。研究对象包括1009例高血压患者和756例血压正常的对照者。数据采用Haplo.Stats和多因素降维（MDR）软件进行分析，风险估计值以比值比（OR）和95%置信区间（95%CI）表示。总体而言，患者与对照者之间rs5804的基因型分布（P = 0.002）和等位基因分布（P = 0.002）存在显著差异。与最常见的单倍型A-C-T-G相比，在对照者中占比过高的单倍型G-C-T-G（P < 0.001）使高血压的粗风险和调整后风险分别降低了36%（OR 0.64；95%CI 0.50 - 0.81；P < 0.001）和39%（OR 0.61；95%CI 0.48 - 0.79；P < 0.001）。进一步的交互分析确定了一个总体最佳的MDR模型，该模型包括rs5804和体重指数（P = 0.001），并通过逻辑回归分析进行了验证。综上所述，我们的研究结果表明SLC12A3基因rs5804在中国东北汉族人群高血压风险的决定中起主要作用。此外，这种多态性与肥胖的交互作用可增强风险预测能力。
