title: Lower ADD1 gene promoter DNA methylation increases the risk of essential hypertension.
abstract: The goal of our study is to investigate the contribution of promoter DNA methylation of α-adducin (ADD1) gene to the risk of essential hypertension (EH). Using the bisulphite pyrosequencing technology, DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured among 33 EH cases and 28 healthy controls. Significantly higher ADD1 DNA methylation levels were observed in the females than in the males (CpG1: P = 0.016; CpG2-5: P = 0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted P = 0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted P = 0.008). CpG1 methylation was inversely correlated with age in females (r = -0.407, P = 0.019) but not in males. ADD1 CpG1 and CpG2-5 methylation levels were significantly lower in post-menopausal (>50 years) women than pre-menopausal (≤50 years) women (CpG1: P = 0.006; CpG2-5: P = 0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age: P = 0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC) = 0.855, P = 0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUC = 0.699, P = 0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, P = 0.001), aspartate aminotransferase (AST, P = 0.005) and uric acid (P<0.001). The concentration of AST was inversely correlated with ADD1 CpG2-5 methylation levels in female controls (r = -0.644, P = 0.024). These observations may bring new hints to elaborate the pathogenesis of EH.
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China. zhanglina@nbu.edu.cn
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhang
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Liu
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Leiting
authors.initials: L
authors.lastname: Xu
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Xin
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Fei
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Zhong
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Limin
authors.initials: L
authors.lastname: Xu
authors.forename: Ling-Mei
authors.initials: LM
authors.lastname: Hao
authors.forename: Xu-Jun
authors.initials: XJ
authors.lastname: Qiu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Le
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*
chemical_list: D051780:Sterol Regulatory Element Binding Protein 1