The 9p21 myocardial infarction high risk locus does not associate with peripheral vascular disease in patients with type 2 diabetes mellitus

Abstract

Chr9p21 locus is a robust CHD genetic marker. Associations were reported with carotid artery plaque, stroke, aneurysms, heart failure, CVD mortality, while no association was found between Chr9p21 and CV risk factors, suggesting that the locus exerts a direct effect on CV risk. We explored the association between the Chr9p21 (SNP rs2383206) and ABI and peripheral artery disease (PAD, i.e. ABI <0.9) in 937 unrelated Italian T2DM (M/F 550, 58.7%/387, 41.3%). Genotyping was performed by TaqMan assay implemented on HT7900 Applied Biosystems platform. Patients were 59.2±7.5 yrs old with a diabetes duration (DD) of 10.4±9.0 yrs, BMI 29.4±5.4 kg/m2; sBP 142±19, dBP 82±10 mmHg, HbA1c 7.7±2.7% (median value 7.45%; first and third quartiles 6.75 and 8.25%); 132 patients (14.1%) had PAD. Genotype distribution was: AA (n. 146) 15.6%; GA (n. 452) 48.2%; GG (n. 339) 36.2%. The sample was in Hardy-Weinberg equilibrium. There was no difference among genotypes in age, DD, smoking, BMI, sBP, dBP, HbA1c, total-, LDL- and HDL-C, triglycerides, uric acid, fibrinogen, urinary A/C ratio and eGFR (MDRD). No association was found between rs2383206 and ABI as a continuous trait (AA: 1.06±0.19; GA: 1.05±0.17; GG: 1.04±0.16; p=NS). Furthermore, no association was apparent between rs2383206 and PAD prevalence (AA 15.1%; GA 13.5%; GG 14.5%; p=0.867). No interaction was observed between rs2383206 and HbA1c above the median value or within the fourth quartile. No differences emerged between genders or in subjects with vs. those without family history of CHD. In logistic backward regressions, PAD was associated with age, sBP, smoking (p<0.0001 for all), dBP (inversely), male gender (p=0.001 for both), HbA1c (p=0.022) and A/C ratio (p=0.035) (model 1) or CHD (p<0.001) (model 2), but not to rs2383206. In this cohort of Italian T2DM, the rs2383206 SNP, previously associated with CHD and shown to interact with glycaemic control, was not associated with continuous ABI and PAD phenotypes.