Impact of Fto Gene Variant on Type 2 Diabetes Mellitus Susceptibility: A Case-Control Study in North Indian Adults

Background: The fat mass and obesity-associated (FTO) gene has been widely studied as a potential genetic determinant of obesity and type 2 diabetes mellitus (T2DM). A single nucleotide polymorphism (SNP), rs9939609, has consistently shown associations with obesity and T2DM in European populations, but data from South Asians, particularly Indians, remain inconclusive. Objective: To investigate the association of FTO gene polymorphism (rs9939609) with T2DM and obesity in adults from North India, and to explore correlations with anthropometric, biochemical, and sociodemographic parameters. Methods: A case-control study was conducted on 320 adults (160 T2DM/obese cases and 160 controls with normal BMI). Anthropometric indices, biochemical markers (HbA1c, lipid profile, blood pressure), and lifestyle factors were recorded. Genotyping for FTO rs9939609 was performed using PCR-RFLP and sequencing. Logistic regression was applied to assess associations. Results: The AT heterozygous genotype was significantly more frequent in cases (41.3%) compared to controls (p=0.03, OR=2.103, 95% CI=1.063–4.159). Subjects with AT genotype had a ~3-fold higher risk of T2DM when HbA1c was abnormal. The variant showed strong associations with obesity (p=0.06, OR=2.008, 95% CI=1.227–3.286), hypertension (p=0.000, r=0.310), and adverse lipid profile (inverse correlation with HDL, OR=0.380, 95% CI=0.229–0.630). Abnormal BMI was more prevalent among females (59.4%), rural residents (65%), smokers (40–49.2%), and non-vegetarians (58.8%). Conclusion: The FTO gene variant rs9939609 significantly influences susceptibility to obesity and T2DM in North Indian adults. The AT genotype appears to confer higher risk, particularly in association with elevated BMI and HbA1c. These findings highlight the gene–environment interaction in the Indian population and suggest FTO as a potential biomarker for T2DM risk stratification.