title: Synergistic effect of smoking with genetic variants in the AMPKα1 gene on the risk of coronary artery disease in type 2 diabetes.
abstract: 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.
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Ruifen
authors.initials: R
authors.lastname: Deng
authors.forename: Shan
authors.initials: S
authors.lastname: Ding
authors.forename: Nan
authors.initials: N
authors.lastname: Gu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Guo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000483:Alleles; D044466:Asian People; D002681:China / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000150:complications / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012907:Smoking / Q000009:adverse effects*
chemical_list: D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human
keywords: AMP-activated protein kinase subunit α1 gene; coronary artery disease; single nucleotide polymorphisms; type 2 diabetes mellitus