Han Liyuan, Liu Panpan, Wang Changyi, Zhong Qilong, Fan Rui, Wang Lin, Duan Shiwei, Zhang Lina
Department of Preventive Medicine and Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
Ningbo Haishu District Center for Disease Control and Prevention, Ningbo, Zhejiang, China.
Hypertens Res. 2015 Apr;38(4):284-90. doi: 10.1038/hr.2014.172. Epub 2015 Jan 8.
The potential effects of the interactions between DNA methylation (CpG1 and CpG2-5 methylation levels) of the α-adducin (ADD1) gene promoter and ADD1 tagSNPs (tag single-nucleotide polymorphisms) or the environmental factors on essential hypertension (EH) risk have not been clarified. Thus, we performed an age- and gender-matched case-control study to investigate the association between ADD1 tagSNPs and EH. A total of 1020 subjects with EH and 1020 normotensive subjects were genotyped by melting temperature shift technology. Logistic regression was used to assess the associations of ADD1 tagSNPs, environmental factors and EH. The generalized multifactor dimensionality reduction (GMDR) method was applied to explore the potential interactions. Under additive, dominant and recessive models, no significant associations were evidenced between EH and rs3755885, rs2071694, rs4963 or rs3775067 with the complete data set or the gender-stratified analysis after adjusting for triglycerides, body mass index and alcohol consumption. However, we observed a significant association between rs4961 and EH under the dominant model after Bonferroni correction when adjusting for confounding factors in the entire sample (odds ratio (OR)=0.64, 95% confidence interval (CI)=0.50-0.83, P=0.001). In GMDR, the two-factor interaction model of alcohol consumption and DNA methylation (CpG1 methylation) was the best model, with a maximum cross-validation consistency of 9/10 and testing balance accuracy of 0.63 (P=0.01). Our results indicate that the SNP rs4961 has a protective role in the development of EH. In conclusion, the interactions between alcohol consumption and DNA methylation (CpG1 methylation) of the ADD1 gene promoter have a significant role in modifying EH susceptibility.
α-内收蛋白（ADD1）基因启动子的DNA甲基化（CpG1和CpG2 - 5甲基化水平）与ADD1标签单核苷酸多态性（tag单核苷酸多态性）或环境因素之间的相互作用对原发性高血压（EH）风险的潜在影响尚未阐明。因此，我们进行了一项年龄和性别匹配的病例对照研究，以调查ADD1标签单核苷酸多态性与EH之间的关联。通过熔解温度偏移技术对总共1020例EH患者和1020例血压正常的受试者进行基因分型。采用逻辑回归评估ADD1标签单核苷酸多态性、环境因素与EH之间的关联。应用广义多因素降维（GMDR）方法探索潜在的相互作用。在加性、显性和隐性模型下，在校正甘油三酯、体重指数和饮酒量后，对于完整数据集或按性别分层分析，EH与rs3755885、rs2071694、rs4963或rs3775067之间均未发现显著关联。然而，在对整个样本中的混杂因素进行校正后，经Bonferroni校正，在显性模型下我们观察到rs4961与EH之间存在显著关联（比值比（OR）=0.64，95%置信区间（CI）=0.50 - 0.83，P = 0.001）。在GMDR中，饮酒与DNA甲基化（CpG1甲基化）的双因素相互作用模型是最佳模型，最大交叉验证一致性为9/10，测试平衡准确率为0.63（P = 0.01）。我们的结果表明，SNP rs4961在EH的发生发展中具有保护作用。总之，饮酒与ADD1基因启动子的DNA甲基化（CpG1甲基化）之间的相互作用在改变EH易感性方面具有重要作用。
