Advances in Clinical and Experimental Medicine
2020, vol. 29, nr 1, January, p. 25–32
Publication type: original article
The association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland
1 Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Poland
2 Department of Social Medicine, Wroclaw Medical University, Poland
3 Department of Pure and Applied Mathematics, Wroclaw University of Science and Technology, Poland
Background. Fat mass and obesity-associated gene (FTO) polymorphism remains the strongest known genetic determinant of common obesity. However, its influence depends on ethnicity, and the FTO-mediated predisposition to other metabolic disturbances is questionable.
Objectives. The aim of our study was to evaluate the association between FTO rs9939609 polymorphism and metabolic syndrome in a population of Prospective Urban Rural Epidemiology (PURE) study in Poland.
Material and Methods. We enrolled 1,097 participants of the PURE study (683 women and 414 men) from the Lower Silesian voivodeship. Anthropometrical parameters and blood pressure were measured. Blood samples were taken for an examination of lipid profile and fasting glucose level. Genomic DNA was isolated and FTO polymorphism rs9939609 was genotyped.
Results. Male A-allele carriers had significantly higher mean body mass, body mass index (BMI), waist-to-hip ratio (WHR), and waist and hip circumferences than men without risk allele. They were also more often diagnosed with obesity on the basis of BMI and central obesity parameters. No such influence was observed in women. There were no significant associations between FTO polymorphism and metabolic syndrome or its components.
Conclusion. Our results suggest a sex-specific association between FTO polymorphism and obesity traits. The occurrence of metabolic syndrome or its components was not related with FTO gene variation in our cohort.
metabolic syndrome, obesity, FTO gene, PURE study
- Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224–2260.
- Dina C, Meyre D, Gallina S, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007;39(6):724–726.
- Frayling TM, Timpson NJ, Weedon MN, 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):889–894.
- Chang Y-C, Liu P-H, Lee W-J, et al. Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes. 2008;57(8):2245–2252.
- Adeyemo A, Chen G, Zhou J, et al. FTO genetic variation and association with obesity in West Africans and African Americans. Diabetes. 2010;59(6):1549–1554.
- Ohashi J, Naka I, Kimura R, et al. FTO polymorphisms in oceanic populations. J Hum Genet. 2007;52(12):1031–1035.
- Li H, Wu Y, Loos RJF, et al. Variants in the fat mass and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes. 2008;57(1):264–268.
- Freathy RM, Timpson NJ, Lawlor DA, et al. Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes. 2008;57(5):1419–1426.
- Hakanen M, Raitakari OT, Lehtimäki T, et al. FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab. 2009;94(4):1281–1287.
- Shimaoka I, Kamide K, Ohishi M, et al. Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese. Hypertens Res. 2010;33(3):214–218.
- Rees SD, Islam M, Hydrie MZI, et al. An FTO variant is associated with type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference: An FTO variant in South Asian populations. Diabet Med. 2011;28(6):673–680.
- Song Y, You N, Hsu Y-H, et al. FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. Obesity (Silver Spring). 2008;16(11):2472–2480.
- Wrzosek M, Zakrzewska A, Ruczko L, Jabłonowska-Lietz B, Nowicka G. Association between rs9930506 polymorphism of the fat mass and obesity-associated (FTO) gene and onset of obesity in Polish adults. Indian J Med Res. 2016;143(3):281–287.
- Gerken T, Girard CA, Tung Y-CL, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 2007;318(5855):1469–1472.
- Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7(12):885–887.
- Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485(7397):201–206.
- Zhao X, Yang Y, Sun B-F, et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 2014;24(12):1403–1419.
- Melhorn SJ, Askren MK, Chung WK, et al. FTO genotype impacts food intake and corticolimbic activation. Am J Clin Nutr. 2018;107(2):145–154.
- Karra E, O’Daly OG, Choudhury AI, et al. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013;123(8):3539–3551.
- Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med. 2008;359(24):2558–2566.
- Kühn AB, Feis D-L, Schilbach L, et al. FTO gene variant modulates the neural correlates of visual food perception. Neuroimage. 2016;128:21–31.
- Merkestein M, Laber S, McMurray F, et al. FTO influences adipogenesis by regulating mitotic clonal expansion. Nat Commun. 2015;6:6792–6801.
- Wahlen K, Wåhlén K, Sjölin E. The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis. J Lipid Res. 2008;49(6):607–611.
- Claussnitzer M, Dankel SN, Kim K-H, et al. FTO obesity variant circuitry and adipocyte browning in humans. N Engl J Med. 2015;373(10):895–907.
- Peng S, Zhu Y, Xu F, Ren X, Li X, Lai M. FTO gene polymorphisms and obesity risk: A meta-analysis. BMC Med. 2011;9:71–86.
- Sobalska-Kwapis M, Suchanecka A, Słomka M, Siewierska-Górska A, Kępka E, Strapagiel D. Genetic association of FTO/IRX region with obesity and overweight in the Polish population. PLoS One. 2017;12(6):e0180295. https://doi.org/10.1371/journal.pone.0180295
- Szkup M, Owczarek AJ, Schneider-Matyka D, Brodowski J, Łój B, Grochans E. Associations between the components of metabolic syndrome and the polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-γ), the fat mass and obesity-associated (FTO), and the melanocortin-4 receptor (MC4R) genes. Aging (Albany NY). 2018;10(1):72–82.
- Łuczyński W, Fendler W, Ramatowska A, et al. Polymorphism of the FTO gene influences body weight in children with type 1 diabetes without severe obesity. Int J Endocrinol. 2014;2014:630712.
- Kowalska I, Malecki MT, Straczkowski M, et al. The FTO gene modifies weight, fat mass and insulin sensitivity in women with polycystic ovary syndrome, where its role may be larger than in other phenotypes. Diabetes Metab. 2009;35(4):328–331.
- Teo K, Chow CK, Vaz M, Rangarajan S, Yusuf S; PURE Investigators-Writing Group. The Prospective Urban Rural Epidemiology (PURE) study: Examining the impact of societal influences on chronic noncommunicable diseases in low-, middle-, and high-income countries. Am Heart J. 2009;158(1):1–7.
- Saldaña-Alvarez Y, Salas-Martínez MG, García-Ortiz H, et al. Gender-dependent association of FTO polymorphisms with body mass index in Mexicans. PLoS One. 2016;11(1):e0145984. doi:10.1371/journal.pone.0145984
- Jess T, Zimmermann E, Kring SII, et al. Impact on weight dynamics and general growth of the common FTO rs9939609: A longitudinal Danish cohort study. Int J Obes (Lond). 2008;32(9):1388–1394.
- Zdrojowy-Wełna A, Zatońska K, Bednarek-Tupikowska G, et al. Determinants of obesity in population of PURE study from Lower Silesia. Endokrynol Pol. 2018;69(6):644–652. doi:10.5603/EP.a2018.0061
- Smemo S, Tena JJ, Kim K-H, et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 2014;507(7492):371–375.
- Landgraf K, Scholz M, Kovacs P, Kiess W, Körner A. FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children: Relevance of FTO variants to defend body weight in lean children? PLoS One. 2016;11(8):e0161739. doi:10.1371/journal.pone.0161739
- Łuczyński W, Zalewski G, Bossowski A. The association of the FTO rs9939609 polymorphism with obesity and metabolic risk factors for cardiovascular diseases in Polish children. J Physiol Pharmacol. 2012;63(3):241–248.
- Ślęzak R, Leszczyński P, Warzecha M, Łaczmański L, Misiak B. Assessment of the FTO gene polymorphisms in male patients with metabolic syndrome. Adv Clin Exp Med. 2018;27(11):1581–1585.
- Legry V, Cottel D, Ferrières J, et al. Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus in the French MONICA study. Metabolism. 2009;58(7):971–975.
- Kalnina I, Zaharenko L, Vaivade I, et al. Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes. Gene. 2013;527(2):462–468.
- Hubacek JA, Dlouha D, Klementova M, Lanska V, Neskudla T, Pelikanova T. The FTO variant is associated with chronic complications of diabetes mellitus in Czech population. Gene. 2018;642:220–224.