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

Authors

  • Iwona Rosset Department of Anthropology, Faculty of Biology and Environmental Protection, University of Łódź, Poland
  • Dominik Strapagiel Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Poland
  • Aneta Sitek Department of Anthropology, Faculty of Biology and Environmental Protection, University of Łódź, Poland
  • Małgorzata Majewska Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Poland
  • Lidia Ostrowska-Nawarycz Department of Biophysics, Chair of Basic and Pre-clinical Sciences, Medical University of Łódź, Poland
  • Elżbieta Żądzińska Department of Anthropology, Faculty of Biology and Environmental Protection, University of Łódź, Poland

DOI:

https://doi.org/10.1515/anre-2016-0002

Keywords:

body mass index, obesity- and overweight-associated gene, FTO, TMEM18, Polish population

Abstract

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.

Downloads

Download data is not yet available.

References

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).
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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

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

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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)
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

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.
View in Google Scholar

Downloads

Published

2016-03-30

How to Cite

Rosset, I., Strapagiel, D., Sitek, A., Majewska, M., Ostrowska-Nawarycz, L., & Żądzińska, E. (2016). Association of FTO and TMEM18 polymorphisms with overweight and obesity in the population of Polish children. Anthropological Review, 79(1), 17–33. https://doi.org/10.1515/anre-2016-0002

Issue

Section

Articles

Most read articles by the same author(s)

1 2 3 > >> 

Similar Articles

1 2 3 4 5 6 7 8 9 10 > >> 

You may also start an advanced similarity search for this article.