title: The interactions between alcohol consumption and DNA methylation of the ADD1 gene promoter modulate essential hypertension susceptibility in a population-based, case-control study.
abstract: 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.
authors.affiliation: Department of Preventive Medicine and Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Han
authors.affiliation: Ningbo Haishu District Center for Disease Control and Prevention, Ningbo, Zhejiang, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Liu
authors.affiliation: Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China.
authors.forename: Changyi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Preventive Medicine and Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Department of Preventive Medicine and Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Preventive Medicine and Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Preventive Medicine and Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Preventive Medicine and Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D019175:DNA Methylation; D000075222:Essential Hypertension; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011153:Population; D011401:Promoter Regions, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D008055:Lipids; D000099291:Adducins