Meta-Analyses of Epigenetics Risk Factors for Heart Disease Prevention: NOS3 Human Gene Variations Across Different Race-Ethnicity Groups

Chang, Nien-Tzu

Purpose: The purpose of this presentation is to disseminate current evidence on population genome health, through meta-analyses of epigenetic risk factors, for heart disease prevention. Ischemic heart disease (IHD) is the major leading cause of deaths worldwide. Epidemiological studies have revealed the association between nitric oxide synthase 3 (NOS3) gene mutation variations with increased risks of IHD in various populations in the world. NOS3 is a gene affects metabolism in the urea cycle of the methylation pathways, critical for preventing systematic inflammation as an epigenetics risk factor for heart health.

Methods: Literature searches, quality scores for the studies, and inter-rater evaluation on data coding was completed to ensure data accuracy for pooled meta-analyses.

Results: Preliminary analyses include a total of 49 case-control studies with13,830 cases and 10,595 controls. The gene mutation variations (GT and TT subtypes) were higher in Caucasians (47.5-64.8%) than Africans (42.9-55.9%), Eurasians (33.9-45.1%), and Asians (13.5–30.7%) across the world, for control and case groups. Pollutions in the world were documented worse in selected European countries from 2004-2009, and in Asia in recent years. Pollution particles smaller than 2.5 micrometers, PM2.5, can pass through lungs, leading to plaque deposits in cardiovascular systems causing systematic inflammation. For lifestyle related meta-analyses, smoking was associated with an increased risk of IHD (24 studies, 6,889 cases, 5,685 controls, RR=1.68, 95% Confidence Interval = 1.39-2.04, p < 0.0001). The history of diabetes mellitus (RR=3.16, 2.4-4.17, P<0.0001) and hyperlipidemia (RR=2.92, 1.97-4.33, p<0.0001) were associated with IHD.

Conclusion: Wild-type GG subtype (52.5% cases, 59.3% controls) was protective against IHD for all populations combined (RR = 0.92, 0.89-0.96, p < 0.0001). Future studies are needed to investigate the interactions between epigenetic risk factors, through methylation pathways, and NOS3 gene variations for cardiovascular health in various populations to prevent IHD.