Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India

Abstract

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer,and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated FOXO3 gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (p = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69–1.26, p > 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (p < 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in FOXO3 (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.