Association between the FTO polymorphic variants and obesity in the Belarusian population
Overweight and obesity refer to the abnormal and excessive deposition of adipose tissue in the human body causing significant harm to health. Unfortunately, there has always been a persisting upward trend in the number of overweight people. The development of obesity may be caused by a combination of excessive food intake, low physical activity, and a hereditary predisposition to it. Studies of the genotypes of obese individuals allowed identifying a number of polymorphic variants of genes that contribute to a genetic predisposition to an excessive weight gain. One of the most significant predictors of obesity is the FTO gene (a fat mass and obesity-associated gene). Genotyping of 655 representatives of the Republic of Belarus was carried out for 13 polymorphic variants of the FTO gene. Genomic DNA extraction was carried out from the peripheral venous blood samples. Real-time PCR was performed for the evaluation of polymorphic variants of the FTO gene. A significant association of the genotype with the body mass index was observed in eight polymorphic variants of the FTO gene: In the carriers of minor homozygotes of polymorphic variants rs11075990, rs1121980, rs1421085, rs17817449, rs3751812, rs9939609, rs9940128, and rs9941349, the body mass index (BMI) was much higher compared with the carriers of corresponding major homozygotes P = 0.0022 – 0.021. An analysis of the linkage disequilibrium of 13 polymorphic variants of the FTO gene was carried out. It was found that eight polymorphic variants of the FTO gene for which a statistically significant association with BMI was shown constitute one block of linkage disequilibrium (r2 = 0.82 – 1.0, P < 0.001) and form two most common haplotypes: A/G/T/T/G/T/G/C (51.9%) and G/A/C/G/T/A/A/T (42.8%). Therefore, to determine the risk for obesity development, it is sufficient to conduct genetic testing for one of these polymorphic variants. This greatly facilitates the process of determining a genetic predisposition to excess weight.
Kopelman PG, 2000, Obesity as a medical problem. Nature, 404: 635–643. https://doi.org/10.1038/35007508
Peeters A, Barendregt JJ, Willekens F, et al., 2003, Obesity in adulthood and its consequences for life expectancy: A life-table analysis. Ann Intern Med, 138: 24–32. https://doi.org/10.7326/0003-4819-138-1-200301070-00008
World Health Organization. Overweight and Obesity Report Fact Sheet. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight [Last accessed on 2023 Jan 27].
UNICEF, World Bank. Levels and Trends in Child Malnutrition: UNICEF-WHO-World Bank Joint Child Malnutrition. Available from: https://www.who.int/publications/i/item/9789240025257 [Last accessed on 2023 Jan 27].
Rolls BJ, 2017, Dietary energy density: Applying behavioural science to weight management. Nutr Bull, 42: 246–253. https://doi.org/10.1111/nbu.12280
Horowitz JF, Klein S, 2000, Lipid metabolism during endurance exercise. Am J Clin Nutr, 72: 558–563. https://doi.org/10.1093/ajcn/72.2.558S
Richter EA, Derave W, Wojtaszewski JF, 2001, Glucose, exercise and insulin: Emerging concepts. J Physiol, 535: 313–322. https://doi.org/10.1111/j.1469-7793.2001.t01-2-00313.x
Gerken T, Girard CA, Tung YC, et al., 2007, The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science, 318: 1469–1472. https://doi:10.1126/science.1151710
Han Z, Niu T, Chang J, et al., 2010, Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature, 464: 1205–1209. https://doi.org/10.1038/nature08921
Frayling TM, Timpson NJ, Weedon MN, et al., 2007, A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science, 316: 889–894. https://doi.org/10.1126/science.1141634
Dina C, Meyre D, Gallina S, et al., 2007, Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet, 39: 724–726. https://doi.org/10.1038/ng2048
Peng S, Zhu Y, Xu F, et al., 2011, FTO gene polymorphisms and obesity risk: A meta-analysis. BMC Med, 9: 71. https://doi.org/10.1186/1741-7015-9-71
Scuteri A, Sanna S, Chen WM, et al., 2007, Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet, 3: 1200–1210. https://doi.org/10.1371/journal.pgen.0030115
Cornes BK, Lind PA, Medland SE, et al., 2009, Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G x E) interaction. Int J Obes (Lond), 33: 75–79. https://doi.org/10.1038/ijo.2008.223
Tan JT, Dorajoo R, Seielstad M, et al., 2008, FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes, 57: 2851–2857. https://doi.org/10.2337/db08-0214
Freathy RM, Timpson NJ, Lawlor DA, et al., 2008, Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes, 57: 1419–1426. https://doi.org/10.2337/db07-1466
Hinney A, Nguyen TT, Scherag A, et al., 2007, Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS One, 2: e1361. https://doi.org/10.1371/journal.pone.0001361
Loos RJ, 2009, Recent progress in the genetics of common obesity. Br J Clin Pharmacol, 68: 811–829. https://doi.org/10.1111/j.1365-2125.2009.03523.x
Solé X, Guinó E, Valls J, et al., 2006, SNPStats: A web tool for the analysis of association studies. Bioinformatics, 22: 1928–1929. https://doi.org/10.1093/bioinformatics/btl268
Dandine-Roulland C, Perdry H, 2018, Manipulation of Genetic Data (SNPs). Computation of GRM and Dominance Matrix, LD, Heritability with Efficient Algorithms for Linear Mixed Model (AIREML). In: Proceedings of the Forty-Sixth European Mathematical Genetics Meeting, 2018. p. 6.
Tan LJ, Zhu H, He H, et al., 2014, Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries. PLoS One, 9: e96149. https://doi.org/10.1371/journal.pone.0096149
Peters U, North KE, Sethupathy P, et al., 2013, A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) study. PLoS Genet, 9: e1003171. https://doi.org/10.1371/journal.pgen.1003171
Rampersaud E, Mitchell BD, Pollin TI, et al., 2008, Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med, 168: 1791–1797. https://doi.org/10.1001/archinte.168.16.1791
Xu Y, Ling J, Yang M, et al., 2014, Rs7206790 and rs11644943 in FTO gene are associated with risk of obesity in Chinese school-age population. PLoS One, 9:e108050. https://doi.org/10.1371/journal.pone.0108050
Li, X., Mei, L., Yang, K., et al., 2009, Identifying association under a previous linkage peak on chromosome 16 for body mass index using cross-sectional and longitudinal data of the Framingham Heart Study. BMC Proc, 3: S101. https://doi.org/10.1186/1753-6561-3-s7-s101
Apalasamy YD, Ming MF, Rampal S, et al., 2012, Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays. Braz J Med Biol Res, 45: 1119–1126. https://doi.org/10.1590/s0100-879x2012007500134