Synergistic effect of smoking with genetic variants in the AMPKα1 gene on the risk of coronary artery disease in type 2 diabetes

摘要

Background: Increasing evidence suggests that adenosine monophosphate-activated protein kinase (AMPK) plays a critical physiological role in the cardiovascular system. The objective of this study was to assess the possible correlation between the genetic variability of the AMPKα1 (PRKAA1) gene and the risk of cardiovascular disease, as well as the interactive effects of the genetic variations and environmental factors, on the risk in Chinese patients with type 2 diabetes. Methods: Five haplotype-tagging single nucleotide polymorphisms (SNPs) at the AMPKα1 locus and 404 unrelated Chinese Han subjects with type 2 diabetes were studied; 260 individuals with coronary artery disease and 144 non-coronary artery disease controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism assay. Results: Minor allele C at rs3805489 was protective from coronary artery disease in type 2 diabetic subjects compared with allele A (OR 0.67, 95% CI 0.48-0.92, p=0.015). There was no significant correlation between the genotypes at five SNPs and the risk of coronary artery disease. In addition, a significant interaction was identified between smoking status and rs3805489 (p=0.018 for interaction). The smokers with genotype AA at the SNP had a three-fold higher risk of coronary artery disease compared with non-smokers with genotypes AC or CC (OR' 3.02, 95% CI' 1.39-6.57, p'=0.005, after adjustment for other known coronary artery disease risk factors). Conclusions: The genetic variability at the AMPKα1 locus has synergetic effects with smoking to increase the risk of coronary artery disease in the Chinese Han population with type 2 diabetes.