title: Elevated PLA2G7 gene promoter methylation as a gender-specific marker of aging increases the risk of coronary heart disease in females.
abstract: PLA2G7 gene product is a secreted enzyme whose activity is associated with coronary heart disease (CHD). The goal of our study is to investigate the contribution of PLA2G7 promoter DNA methylation to the risk of CHD. Using the bisulphite pyrosequencing technology, PLA2G7 methylation was measured among 36 CHD cases and 36 well-matched controls. Our results indicated that there was a significant association between PLA2G7 methylation and CHD (adjusted P = 0.025). Significant gender-specific correlation was observed between age and PLA2G7 methylation (males: adjusted r = -0.365, adjusted P = 0.037; females: adjusted r = 0.373, adjusted P = 0.035). A breakdown analysis by gender showed that PLA2G7 methylation was significantly associated with CHD in females (adjusted P = 0.003) but not in males. A further two-way ANOVA analysis showed there was a significant interaction between gender and status of CHD for PLA2G7 methylation (gender*CHD: P = 6.04E-7). Moreover, PLA2G7 methylation is associated with the levels of total cholesterols (TC, r = 0.462, P = 0.009), triglyceride (TG, r = 0.414, P = 0.02) and Apolipoprotein B (ApoB, r = 0.396, P = 0.028) in females but not in males (adjusted P>0.4). Receiver operating characteristic (ROC) curves showed that PLA2G7 methylation could predict the risk of CHD in females (area under curve (AUC) = 0.912, P = 2.40E-5). Our results suggest that PLA2G7 methylation changes with aging in a gender-specific pattern. The correlation between PLA2G7 methylation and CHD risk in females is independent of other parameters including age, smoking, diabetes and hypertension. PLA2G7 methylation might exert its effects on the risk of CHD by regulating the levels of TC, TG, and ApoB in females. The gender disparities in the PLA2G7 methylation may play a role in the molecular mechanisms underlying the pathophysiology of CHD.
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Danjie
authors.initials: D
authors.lastname: Jiang
authors.forename: Dawei
authors.initials: D
authors.lastname: Zheng
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Haibo
authors.initials: H
authors.lastname: Liu
authors.forename: Leiting
authors.initials: L
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Liao
authors.forename: Panpan
authors.initials: P
authors.lastname: Liu
authors.forename: Xinbao
authors.initials: X
authors.lastname: Shi
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Wang
authors.forename: Lebo
authors.initials: L
authors.lastname: Sun
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Zhou
authors.forename: Ni
authors.initials: N
authors.lastname: Li
authors.forename: Limin
authors.initials: L
authors.lastname: Xu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Le
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.forename: Guofeng
authors.initials: G
authors.lastname: Shao
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000368:Aged; D000375:Aging; D001055:Apolipoproteins B / Q000378:metabolism; D019540:Area Under Curve; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054467:Phospholipases A2 / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012307:Risk Factors; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D014280:Triglycerides; D002784:Cholesterol; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
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