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  1. Lin, Yen-Chun
  2. Nunez, Veronica
  3. Johns, Robin
  4. Shiao, S. Pamela K.


Background: Apolipoprotein A5 (APOA5) 1131 is one of the most investigated gene polymorphisms in association with cardiovascular diseases (CVD) for its roles in epigenetics pathways.


Objectives: The major objective of this metaprediction study was to comprehensively examine the association of polymorphism risk subtypes of APOA5 1131 gene and potential contributing factors of CVD risks in global populations.


Methods: This study is a meta-analysis to determine APOA5 gene polymorphisms as risk factors for CVDs. Following the guidelines of meta-analyses, we applied big data analytics including the recursive partition tree, nonlinear association curve fit, and heat maps for data visualization-in addition to the conventional pooled analyses.


Results: A total of 17,692 CVD cases and 23,566 controls from 50 study groups were included. The frequency of APOA5 1131 CC and TC polymorphisms in Asian populations (22.2%-52.6%) were higher than that in other populations, including Caucasians and Eurasians (10.0%-25.0%). The homozygous CC and heterozygous TC genotypes (both p < .0001) were associated with increased risks for CVD and were higher in many Western nations, including Canada, Spain, the Czech Republic, Hungary, Turkey, Egypt, France, and Iran. The CC genotype was associated with greater risks (RR > 2.00, p < .0001) for dyslipidemia and myocardial infarction, whereas RR > 1.00 was associated with metabolic syndrome, coronary artery disease, and stroke. Air pollution was significantly associated with APOA5 1131 CC and TC polymorphisms.


Discussion: The findings of this study provided novel insight to further understand the associations among APOA5 1131 polymorphisms, air pollution, and the development of CVDs. Methylation studies are needed to examine epigenetic factors associated with APOA5 1131 polymorphisms and CVD and to suggest potential prevention strategies for CVD.