title: Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
abstract: BACKGROUND
  Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary atherosclerosis are uncertain. We therefore investigated the association between TCF7L2 polymorphisms and angiographically determined CAD in diabetic and non-diabetic patients.
  
  
  RESULTS
  We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses ≥50%. Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive OR = 1.29 [1.09-1.53]; p = 0.003). This association was strong and significant in T2DM patients (n = 393; OR = 1.91 [1.32-2.75]; p = 0.001) but not in non-diabetic subjects (OR = 1.09 [0.90-1.33]; p = 0.370). The interaction risk allele by T2DM was significant (p(interaction) = 0.002), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rs12255372 and rs11196205 were also significantly associated with CAD in diabetic patients (adjusted additive OR = 1.90 [1.31-2.74]; p = 0.001 and OR = 1.75 [1.22-2.50]; p = 0.002, respectively). Further, haplotype analysis demonstrated that haplotypes including the rare alleles of all investigated variants were significantly associated with CAD in the whole cohort as well as in diabetic subjects (OR = 1.22 [1.04-1.43]; p = 0.013 and OR = 1.67 [1.19-2.22]; p = 0.003, respectively).
  
  
  CONCLUSIONS
  These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM. TCF7L2 therefore appears as a genetic link between diabetes and atherosclerosis.
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Saely
authors.forename: Simone
authors.initials: S
authors.lastname: Geller-Rhomberg
authors.forename: Gudrun
authors.initials: G
authors.lastname: Sonderegger
authors.forename: Philipp
authors.initials: P
authors.lastname: Rein
authors.forename: Thomas
authors.initials: T
authors.lastname: Winder
authors.forename: Stefan
authors.initials: S
authors.lastname: Beer
authors.forename: Alexander
authors.initials: A
authors.lastname: Vonbank
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
mesh_terms: D000368:Aged; D015331:Cohort Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003925:Diabetic Angiopathies / Q000150:complications* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein