1704-P: SIRT1 rs7896005 SNP and Incidence of Major Vascular Events in Type 2 Diabetes: A 13-Year, Single-Centre, Follow-Up Study

Genetic variants of SIRT1, in particular the G allele of the rs7896005 SNP, are associated with increased risk for T2DM. We recently reported that this SNP was not associated with all-cause mortality over a 13-year follow-up. We are now exploring the association of this SNP with incidence of major CV events in 917 T2DM (98.6% of the original cohort). Incidence data were obtained by interrogating hospital discharge registers. Genotypes distribution was: AA, n. 83 (9.1%), AG, n. 397 (43.3%), GG, n. 437 (47.7%). MAF was 0.307 and Hardy-Weinberg equilibrium met (chi-square 0.2809, p=0.596). There was no difference across genotypes for major CV risk factors and treatments. Over 11.25±4.40 years, 261 major CV events occurred (28.5%): AA/AG n. 121, 25.2%; GG n. 140, 32.0% (K-M logrank 5.798, p=0.016). After adjustment for age, sex, DD, BMI, HbA1c, A/C ratio, eGFR (CKD-EPI), smoking, hypertension, dyslipidemia, retinopathy, peripheral neuropathy and prior CV events, HR of GG vs. AA/AG was 1.28 (95% CI 1.00-1.65, p=0.047). Over 11.81±4.06 years, 176 coronary events occurred (19.2%): AA/AG n. 77, 16.0%; GG n. 99, 22.7% (K-M logrank 7.093, p=0.008). After adjustment, HR vs. AA/AG was 1.47 (1.09-2.00, p=0.013). A total of 81 (8.8%) hospitalization for heart failure (HF) occurred over a follow-up of 12.75±3.11 years: AA/AG n. 33, 6.9%; GG n. 48, 11.0% (K-M logrank 4.999, p=0.025). After correction, HR vs. AA/AG was 1.54 (0.98-2.42, p=0.063). Finally, over 12.92±2.95 years, 36 peripheral vascular events occurred (3.9%): AA/AG n. 11, 2.3%; GG n. 25, 5.7% (K-M logrank 7.320, p=0.007). After adjustment, HR vs. AA/AG was 2.15 (1.02-4.50, p=0.043). No association was found with cerebrovascular events and ESRD. With the limitations of the relatively small sample size, but the strength of the long-term observation, we suggest that in T2DM rs7896005 A/G SNP of SIRT1 is independently associated with incidence of major CV, coronary and peripheral vascular events and also with hospitalization for heart failure.