title: Polymorphism on chromosome 9p21.3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients.
abstract: BACKGROUND
  Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways.
  
  
  METHODS
  Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A(1c) (HbA(1c)), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype.
  
  
  RESULTS
  The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR: 1.270, P = 0.044) and non-diabetic (OR: 1.369, P = 0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P = 0.019), but not in non-diabetics (P = 0.126). Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD (OR: 2.367, P = 0.008) and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80 ± 17.20 vs. 23.09 ± 21.63, P = 0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA(1c), or inflammatory cytokines for diabetic or non-diabetic patients with CAD.
  
  
  CONCLUSIONS
  This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Peng
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Rui-Yan
authors.initials: RY
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ling-Jie
authors.initials: LJ
authors.lastname: Wang
authors.forename: Qiu-Jing
authors.initials: QJ
authors.lastname: Chen
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Shen
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha