Longevity-Associated Forkhead Box O3 (FOXO3) Single Nucleotide Polymorphisms are Associated with Type 2 Diabetes...

BACKGROUND This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) of Forkhead box O3 (FOXO3) gene with type 2 diabetes mellitus (T2D). MATERIAL AND METHODS A total of 843 elderly residents from east China were enrolled in this study, which included 426 patients with type 2 diabetes and 417 controls. Four SNPs were analyzed by qPCR. Genotype frequencies of the 4 SNPs in FOXO3 of the patients and controls were analyzed using logistic regression analysis. The association between each SNP and clinical indicators was analyzed by linear regression analysis. RESULTS None of the 4 FOXO3 variants, rs13217795, rs2764264, rs2802292, and rs13220810, were associated with the risk of type 2 diabetes compared to controls. However, rs13217795, rs2764264, and rs2802292 were associated with lower blood glucose levels. Notably, further subgroup analysis indicated that the longevity-associated alleles of FOXO3 SNP (rs13217795, rs2764264, and rs2802292) were associated with lower blood glucose levels in women (TC versus TT, -0.724 mmol/L, P=0.005; CC versus TT, -1.093 mmol/L, P=0.03; TC versus TT, -0.801 mmol/L, P=0.002; CC versus TT, -1.212 mmol/L, P=0.001; TG versus TT, -0.754 mmol/L, P=0.004; and GG versus TT, -1.150 mmol/L, P=0.001) but not in men. CONCLUSIONS The results indicated that longevity-associated FOXO3 variants were correlated with lower blood glucose levels in elderly women with type 2 diabetes in east China.