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<p>Genetic factors have been implicated in the susceptibility to type 2 diabetes mellitus (T2DM). The fat mass and obesity-associated (FTO) gene, particularly the rs9939609 variant, has been extensively examined in relation to measures of adiposity, which are frequently observed in individuals with T2DM. In this context, rs9939609 has primarily been studied for its association with obesity-related traits that may, in turn, relate to metabolic abnormalities in T2DM. However, evidence describing this adiposity-mediated relationship remains limited in North Indian populations. A case–control study was conducted including 120 newly diagnosed, treatment-naive T2DM patients and 120 age- and sex-matched healthy controls. Genotyping of the FTO rs9939609 polymorphism was performed using PCR–RFLP. Anthropometric measurements, blood pressure, and biochemical parameters including fasting blood glucose and lipid profile were assessed. Statistical analyses included chi-square tests, ANOVA, binary logistic regression, and linear regression models. The frequency of the rs9939609 A allele and AA/AT genotypes was higher among cases compared with controls. Individuals carrying the A allele showed higher values of waist circumference, fasting blood glucose, and triglycerides. In crude logistic regression analysis, rs9939609 was associated with Type 2 Diabetes Mellitus (T2DM) under additive and dominant genetic models; however, these associations were attenuated and did not remain statistically significant after adjustment for body mass index. Linear regression analysis showed associations between the A allele and waist circumference, fasting blood glucose, and triglyceride levels, with low to modest explained variance. No statistically significant associations were observed with systolic or diastolic blood pressure and high-density lipoprotein cholesterol. The FTO rs9939609 polymorphism is associated with central adiposity and adverse metabolic traits in North Indian individuals with T2DM. Its crude association with T2DM is largely attenuated after adjustment for adiposity, indicating that the observed metabolic effects are predominantly mediated through obesity-related pathways rather than representing an independent genetic risk for T2DM.</p>

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Association of FTO rs9939609 Gene Polymorphism with Metabolic Abnormalities in Type 2 Diabetes Mellitus: Evidence from a North Indian Population

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • Dinesh Kumar,
  • Jyoti Batra,
  • Abhishek Pandeya,
  • Juhi Aggarwal,
  • Sudeep Kumar

摘要

Genetic factors have been implicated in the susceptibility to type 2 diabetes mellitus (T2DM). The fat mass and obesity-associated (FTO) gene, particularly the rs9939609 variant, has been extensively examined in relation to measures of adiposity, which are frequently observed in individuals with T2DM. In this context, rs9939609 has primarily been studied for its association with obesity-related traits that may, in turn, relate to metabolic abnormalities in T2DM. However, evidence describing this adiposity-mediated relationship remains limited in North Indian populations. A case–control study was conducted including 120 newly diagnosed, treatment-naive T2DM patients and 120 age- and sex-matched healthy controls. Genotyping of the FTO rs9939609 polymorphism was performed using PCR–RFLP. Anthropometric measurements, blood pressure, and biochemical parameters including fasting blood glucose and lipid profile were assessed. Statistical analyses included chi-square tests, ANOVA, binary logistic regression, and linear regression models. The frequency of the rs9939609 A allele and AA/AT genotypes was higher among cases compared with controls. Individuals carrying the A allele showed higher values of waist circumference, fasting blood glucose, and triglycerides. In crude logistic regression analysis, rs9939609 was associated with Type 2 Diabetes Mellitus (T2DM) under additive and dominant genetic models; however, these associations were attenuated and did not remain statistically significant after adjustment for body mass index. Linear regression analysis showed associations between the A allele and waist circumference, fasting blood glucose, and triglyceride levels, with low to modest explained variance. No statistically significant associations were observed with systolic or diastolic blood pressure and high-density lipoprotein cholesterol. The FTO rs9939609 polymorphism is associated with central adiposity and adverse metabolic traits in North Indian individuals with T2DM. Its crude association with T2DM is largely attenuated after adjustment for adiposity, indicating that the observed metabolic effects are predominantly mediated through obesity-related pathways rather than representing an independent genetic risk for T2DM.