上皮钠通道基因与血压变化及高血压发病率的关联：GenSalt研究
Associations of epithelial sodium channel genes with blood pressure changes and hypertension incidence: the GenSalt study.
作者信息
Yang Xueli, He Jiang, Gu Dongfeng, Hixson James E, Huang Jianfeng, Rao Dabeeru C, Shimmin Lawrence C, Chen Jichun, Rice Treva K, Li Jianxin, Schwander Karen, Kelly Tanika N
机构信息
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of 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, Louisiana; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana;
出版信息
Am J Hypertens. 2014 Nov;27(11):1370-6. doi: 10.1093/ajh/hpu060. Epub 2014 Apr 15.
BACKGROUND
We examined the associations of epithelial sodium channel (ENaC) genes with blood pressure (BP) changes and hypertension incidence in a longitudinal family study.
METHODS
A total of 2,755 Han Chinese participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) baseline examination were eligible for this study. The associations of 43 tag single nucleotide polymorphisms (SNPs) in ENaC genes with BP changes and hypertension incidence were assessed using mixed models to account for the correlations of repeated measures among individuals and within families. A genotype by time interaction term was used to model differences in longitudinal BP change according to genotype over time. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses.
RESULTS
During an average of 7.4 years follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and approximately 33% of participants developed hypertension. SCNN1A SNP rs11064153 and SCNN1G SNP rs4401050 were significantly associated with longitudinal changes in SBP after adjustment for multiple testing (P interaction = 5.8×10(-4) and 0.001, respectively). Similar but nonsignificant trends were observed for the associations between both rs11064153 and rs4401050 and DBP changes (P interaction = 0.024 and 0.005, respectively) and between rs11604153 and hypertension incidence (P = 0.02). Gene-based analyses also supported the overall association of SCNN1G with longitudinal changes in SBP (P = 2.0×10(-4)).
CONCLUSIONS
Our findings indicated that SCNN1A and SCNN1G may contribute to BP changes over time in the Han Chinese population. Replication of these findings is warranted.
背景
在一项纵向家庭研究中，我们研究了上皮钠通道（ENaC）基因与血压（BP）变化及高血压发病率之间的关联。
方法
共有2755名参加盐敏感性遗传流行病学网络（GenSalt）基线检查的汉族参与者符合本研究条件。使用混合模型评估ENaC基因中43个标签单核苷酸多态性（SNP）与BP变化及高血压发病率之间的关联，以考虑个体间和家庭内重复测量的相关性。采用基因型与时间交互项来模拟纵向BP变化随基因型随时间的差异。使用截短乘积法进行基于基因的分析。在所有分析中均采用Bonferroni法对多重检验进行校正。
结果
在平均7.4年的随访期间，收缩压（SBP）和舒张压（DBP）升高，约33%的参与者患高血压。在进行多重检验校正后，SCNN1A SNP rs11064153和SCNN1G SNP rs4401050与SBP的纵向变化显著相关（交互P值分别为5.8×10⁻⁴和0.001）。rs11064153和rs4401050与DBP变化之间的关联（交互P值分别为0.024和0.005）以及rs11604153与高血压发病率之间的关联（P = 0.02）观察到相似但不显著的趋势。基于基因的分析也支持SCNN1G与SBP纵向变化的总体关联（P = 2.0×10⁻⁴）。
结论
我们的研究结果表明，SCNN1A和SCNN1G可能在汉族人群中随时间推移对BP变化有影响。这些发现值得重复验证。
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