IMPACT OF FTO GENE VARIANT ON TYPE 2 DIABETES MELLITUS SUSCEPTIBILITY: A CASE-CONTROL STUDY IN NORTH INDIAN ADULTS
Main Article Content
Keywords
FTO gene , rs9939609, Obesity, North Indian population, Case-control study
Abstract
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.
References
2. International Diabetes Federation. IDF Diabetes Atlas, 10th ed. Brussels: IDF; 2021.
3. Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK, et al. Prevalence of diabetes and prediabetes in 15 states of India: results from the ICMR–INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol. 2017;5(8):585–96.
4. Hu FB. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care. 2011;34(6):1249–57.
5. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889–94.
6. Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007;39(6):724–6.
7. Sachan A. A molecular analysis of FTO gene polymorphism in patients of obesity and its correlation with biochemical & anthropometric measurements of adults in the population of Kanpur & nearby areas [PhD thesis]. Kanpur: Rama University; 2017.
8. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007;3(7):e115.
9. Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009;41(1):18–24.
10. Willer CJ, Speliotes EK, Loos RJF, Li S, Lindgren CM, Heid IM, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009;41(1):25–34.
11. Sanghera DK, Ortega L, Han S, Singh J, Ralhan SK, Wander GS, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: replication study in 3,561 individuals. Diabetes. 2008;57(1):123–8.
12. Yajnik CS, Janipalli CS, Bhaskar S, Kulkarni SR, Freathy RM, Prakash S, et al. FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia. 2009;52(2):247–52.
13. Ramya K, Radha V, Ghosh S, Majumder PP, Mohan V. Genetic variations in the FTO gene are associated with obesity and type 2 diabetes in South Indians (CURES-79). Diabetes Technol Ther. 2011;13(1):33–42.
14. Chauhan G, Tabassum R, Mahajan A, Dwivedi OP, Mahendran Y, Kaur I, et al. Common variants of FTO and the risk of obesity and type 2 diabetes in Indians. J Hum Genet. 2011;56(9):720–6.
15. Janipalli CS, Kumar MVK, Vinay DG, Sandeep MN, Sreenivas D, Banerjee S, et al. Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of type 2 diabetes and obesity in Indian population. Hum Genet. 2012;131(7):1057–69.
16. Dwivedi OP, Tabassum R, Chauhan G, Ghosh S, Marwaha RK, Tandon N, et al. Common variants of FTO are associated with childhood obesity in a cross-sectional study of 3,126 urban Indian children. PLoS One. 2012;7(10):e47772.
17. Bansal A, Dwivedi OP, Dasgupta S, Saboo B, Chawla R, Kumar M, et al. Association of common genetic variants with obesity and metabolic traits in Indian population. Diabetes Metab Syndr. 2019;13(1):688–94.
18. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889–94.
19. Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007;39(6):724–6.
20. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007;3(7):e115.
21. Willer CJ, Speliotes EK, Loos RJF, Li S, Lindgren CM, Heid IM, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009;41(1):25–34.
22. Sanghera DK, Ortega L, Han S, Singh J, Ralhan SK, Wander GS, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: replication study in 3,561 individuals. Diabetes. 2008;57(1):123–8.
23. Yajnik CS, Janipalli CS, Bhaskar S, Kulkarni SR, Freathy RM, Prakash S, et al. FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia. 2009;52(2):247–52.
24. Ramya K, Radha V, Ghosh S, Majumder PP, Mohan V. Genetic variations in the FTO gene are associated with obesity and type 2 diabetes in South Indians (CURES-79). Diabetes Technol Ther. 2011;13(1):33–42.
25. Chauhan G, Tabassum R, Mahajan A, Dwivedi OP, Mahendran Y, Kaur I, et al. Common variants of FTO and the risk of obesity and type 2 diabetes in Indians. J Hum Genet. 2011;56(9):720–6.
26. Janipalli CS, Kumar MVK, Vinay DG, Sandeep MN, Sreenivas D, Banerjee S, et al. Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of type 2 diabetes and obesity in Indian population. Hum Genet. 2012;131(7):1057–69.
27. Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 2007;318(5855):1469–72.
28. Wardle J, Llewellyn C, Sanderson S, Plomin R. The FTO gene and measured food intake in children. Int J Obes. 2009;33(1):42–5.
29. Hardy R, Wills AK, Wong A, Elks CE, Wareham NJ, Loos RJ, et al. Life course variations in the associations between FTO and obesity traits in a British birth cohort. PLoS One. 2010;5(11):e13961.
30. Haupt A, Thamer C, Machann J, Kirchhoff K, Stefan N, Tschritter O, et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity. 2008;16(8):1969–72.
31. Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK, et al. Prevalence of diabetes and prediabetes in 15 states of India: results from the ICMR–INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol. 2017;5(8):585–96