Association of FTO and TMEM18 polymorphisms with overweight and obesity in the population of Polish children

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The objective of the study was to verify whether or not FTO rs9939609, rs9926289 and TMEM18 rs4854344, rs6548238, rs2867125 variants are important risk factors for overweight and/or obesity in Polish children aged 6-16 (n=283). FTO rs 9939609 and rs9926289 exhibited a strong codominant obesity-predisposing effect of genotypes homozygous for minor alleles (OR=5.42, 95% CI: 2.04-14.39, p=0.0006). The important finding of the study is increased risk of overweight (OR=5.03, 95% CI: 1.15-21.93, p=0.0306) in individuals homozygous for the minor alleles rs4854344, rs6548238 and rs2867125 in the recessive inheritance model, while no other significant associations between TMEM18 variants and risk of obesity were found. Given the identified interaction TMEM18 genotype × BMI category (p=0.0077), it seems that the effect of homozygous for the minor alleles may be compared to a “weight guard”, which significantly increases the risk of overweight, but not of obesity, because it promotes weight gain only up to the threshold of obesity. Conclusion: The proposed hypothetical effect (“weight guard”) of homozygous for the minor alleles in the TMEM18 based on a rather small sample is a possible explanation of the effects of minor alleles, which minimize the risk of obesity.

Almen MS, Jacobsson JA, Shaik JH, Olszewski PK, Cedernaes J, Alsio J, et al. 2010. The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children. BMC Med Genet 11(58).

Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN. 2008. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 359(24):2558-66.

Chrzanowska M, Koziel S, Ulijaszek SJ. 2007. Changes in BMI and the prevalence of overweight and obesity in children and adolescents in Cracow, Poland, 1971-2000. Econ Hum Biol 5(3):370-8.

Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. 2000. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320(7244):1240-3.

Cole TJ, Green PJ. 1992. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 11(10):1305-19.

Cole TJ, Lobstein T. 2012. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. PediatrObes 7(4):284-94.

Field SF, Howson JM, Walker NM, Dunger DB, Todd JA. 2007. Analysis of the obesity gene FTO in 14,803 type 1 diabetes cases and controls. Diabetologia 50(10):2218-20.

Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, 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(5826):889-94.

Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, et al. 2007. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318(5855):1469-72.

Graff M, North KE, Mohlke KL, Lange LA, Luo J, Harris KM, et al. 2012. Estimation of genetic effects on BMI during adolescence in an ethnically diverse cohort: The National Longitudinal Study of Adolescent Health. Nutr Diabetes 2:e47.

Hardy R, Wills AK, Wong A, Elks CE, Wareham NJ, Loos RJ, et al. 2010. Life course variations in the associations between FTO and MC4R gene variants and body size. Hum Mol Genet 19(3):545-52.

Holzapfel C, Grallert H, Huth C, Wahl S, Fischer B, Doring A, et al. 2010. Genes and lifestyle factors in obesity: results from 12,462 subjects from MONICA/KORA. Int J Obes (Lond) 34(10):1538-45.

Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, et al. 2009. Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. J Hum Genet 54(12):727-31.

Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R, et al. 2008. Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 53(6):546-53.

Knussmann R. 1988. Anthropologie. Handbuch der vergleichendenBiologie der Menschen. Band I. Wesen und Methoden der Antropologie. Stuttgart.

Kozieł S, Welon Z, Bielicki T, Szklarska A, Ulijaszek S. 2004. The effect of the economic transition on the body mass index of conscripts in Poland. Econ Hum Biol 2(1):97-106.

Kozieł S. 2005. What is the risk for overweight children of being overweight at the age of 18 years? The Wrocław Growth Study. Przegląd Antropologiczny - Anthropol Rev 68: 43-52.

Łuczyński W, Zalewski G, Bossowski A. 2012. The association of the FTO rs9939609 polymorphism with obesity and metabolic risk factors for cardiovascular diseases in Polish children. J PhysiolPharmacol 63(3):241-8.

Ohashi J, Naka I, Kimura R, Natsuhara K, Yamauchi T, Furusawa T, et al. 2007. FTO polymorphisms in oceanic populations. J Hum Genet 52(12):1031-5.

Pan H, Cole T. 2011. LMS growth a Microsoft Excel add-in to access growth references based on the LMS method. (Version 2.74).

Rampersaud E, Mitchell BD, Pollin TI, Fu M, Shen H, O’Connell JR, et al. 2008. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 168(16):1791-7.

Rask-Andersen M, Jacobsson JA, Moschonis G, Chavan RA, Sikder MA, Allzen E, et al. 2012. Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats. Eur J Hum Genet 20(2):192-7.

Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, Hallmans G, et al. 2009. Replication and extension of genome- wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet 18(8):1489-96.

Rosset I, Roślak M, Grabowska J, Borowska- Strugińska B, Lorkiewicz W, Sitek A, et al. 2009. The state of physical development of children in Łódź. In Żądzińska E (Ed.), Dziecko łódzkie 2004. Normy rozwoju biologicznego. (pp. 39-142). Łódź: Wydawnictwo Uniwersytetu Łódzkiego. (in polish)

Rosskopf D, Schwahn C, Neumann F, Bornhorst A, Rimmbach C, Mischke M, et al. 2011. The growth hormone--IGF-I axis as a mediator for the association between FTO variants and body mass index: results of the Study of Health in Pomerania. Int J Obes (Lond) 35(3):364-72.

Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, et al. 2007. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3(7):e115.

Sitek A, Rosset I, Strapagiel D, Majewska M, Ostrowska-Nawarycz L, Żądzińska E. 2014. Association of FTO gene with obesity in Polish schoolchildren. Anthropol Rev 77(1):33-44.

Tan JT, Dorajoo R, Seielstad M, Sim XL, Ong RT, Chia KS, et al. 2008. FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 57(10):2851-7.

Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al. 2009. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 41(1):18-24.

Wahlen K, Sjolin E, Hoffstedt J. 2008. The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis. J Lipid Res 49(3):607-11.

Wardle J, Carnell S, Haworth CM, Farooqi IS, O’Rahilly S, Plomin R. 2008. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 93(9):3640-3.

Wardle J, Carnell S, Haworth CM, Plomin R. 2008. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am J ClinNutr 87(2):398-404.

Wardle J, Llewellyn C, Sanderson S, Plomin R. 2009. The FTO gene and measured food intake in children. Int J Obes (Lond) 33(1):42-5.

Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, et al. 2009. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41(1):25-34.

Żądzińska E, Rosset I, Kozieł S, Nawarycz T, Borowska-Strugińska B, Lorkiewicz W, et al. 2012. Frequency of under- and overweight among children and adolescents during the economic transition in Poland. Homo 63(3): 216-32.

Zhang M, Zhao X, Cheng H, Wang L, Xi B, Shen Y, et al. 2014. Age- and sex-dependent association between FTO rs9939609 and obesity-related traits in Chinese children and adolescents. PLoS One 9(5):e97545.

Zhao J, Bradfield JP, Li M, Wang K, Zhang H, Kim CE, et al. 2009. The role of obesity- associated loci identified in genomewide association studies in the determination of pediatric BMI. Obesity (Silver Spring)17(12):2254-7.

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