Elevated PLA2G7 gene promoter methylation as a gender-specific marker of aging increases the risk of coronary heart disease in females

• Published in: PloS one Vol. 8; no. 3; p. e59752
• Main Authors: Jiang, Danjie, Zheng, Dawei, Wang, Lingyan, Huang, Yi, Liu, Haibo, Xu, Leiting, Liao, Qi, Liu, Panpan, Shi, Xinbao, Wang, Zhaoyang, Sun, Lebo, Zhou, Qingyun, Li, Ni, Xu, Limin, Le, Yanping, Ye, Meng, Shao, Guofeng, Duan, Shiwei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.03.2013; Public Library of Science (PLoS)
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Aging; Apolipoprotein B; Apolipoproteins; Apolipoproteins B - metabolism; Area Under Curve; Biology; Blood platelets; Cardiovascular disease; Cardiovascular diseases; Case-Control Studies; Cholesterol - blood; Coronary artery disease; Coronary Artery Disease - genetics; Coronary Disease - genetics; Correlation; Deoxyribonucleic acid; Diabetes mellitus; DNA; DNA Methylation; Enzymes; Female; Females; Gender; Gene expression; Health risk assessment; Health risks; Heart; Heart diseases; Hospitals; Humans; Hypertension; Laboratories; Lipoproteins; Male; Males; Maternal & child health; Medicine; Middle Aged; Molecular modelling; Phospholipases A2 - genetics; Phospholipases A2 - metabolism; Plasma; Promoter Regions, Genetic; Risk Factors; ROC Curve; Sex Factors; Smoking; Studies; Triglycerides - blood; Variance analysis; Womens health; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059752

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.