Association of LPA Gene Copy Number Variation and Apolipoprotein E Polymorphism in Young AMI

Abstract

Acute myocardial infarction (AMI) is the most severe manifestation of coronary artery disease which is the leading cause of death globally. In Malaysia, there is an increasing number of AMI among young patients aged less than 45 years. The presentation of AMI at younger age suggests the possibility of genetic predisposition. Since LPA and APOE genes are known to be involved in lipid metabolism, they may contribute to the development of atherosclerosis leading to AMI. However, to date, there is no reported study on the association of LPA copy number variations (CNV) and APOE polymorphism with AMI in young patients. The aim of the current study is to assess the association of LPA CNV and APOE polymorphism with AMI in young adults. This study was conducted on 40 men grouped into 20 young acute myocardial infarction (YAMI) patients and 20 healthy controls. DNAs were purified from blood. The APOE genotyping was performed using multiplex PCR technique while LPA CNV was performed using digital PCR and the analysis of copy number was performed using QIAcuity Software Suite version 1.2 (QIAgen, Germany). Chi –square and Kruskall-wallis tests were used for data analysis. In order to improve the statistical power to signify the role of APOE polymorphism in CAD, meta-analyses were performed from this current result and selected studies among Asian populations using Comprehensive Meta-analysis version 3 software program. No significant association of LPA CNV with AMI was found (p = 0.459) in young adults. Although APOE genotypes and alleles were not significantly associated with AMI in young adults (p=0.484), this study found that E3/E3 genotypes and e3 allele were the commonest genotypes and allele. Lipid parameters were also found to be not significantly associated with LPA CNV status as well as APOE genotypes. However, from the current meta-analysis, APOE genotypes of E3/E3 was found to be protective whilst E3/E4 and e4 allele were found to increase the risk of CAD. In conclusion, this study found that there was no association of LPA CNV and APOE polymorphism with AMI in young adults, but the meta-analysis reaffirmed the role of APOE genotypes and e4 allele in the development of CAD. In pursuance of assessing the contribution of LPA gene CNV and APOE genotypes to our local population, a larger sample representation is recommended.