Association of FTO gene with obesity in Polish schoolchildren

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Abstract

The goal of the study was verification of fat mass and obesity-associated (FTO) gene polymorphisms as significant risk factors of obesity in the population of Polish children. Body mass index (BMI) and DNA were evaluated, where DNA was extracted from saliva, collected from 213 children at the age of 6-13 years. DNA was genotyped by PCR (polymerase chain reaction) and HRM (high resolution melting) techniques, as well as by direct sequencing. Three (3) FTO polymorphisms were identified: rs9939609, rs9926289 and rs76804286, the last polymorphism located between the first two. For the first time, absolute linkage disequilibrium (LD) of FTO gene rs9939609 and rs9926289 polymorphisms was confirmed in data for the Polish population (D’=1, r2=1). The lack of a complete dependence among the three single nucleotide polymorphisms (SNPs) of the FTO gene was a consequence of the concurrence of homozygotes with minor alleles A of rs9939609+rs9926289 of FTO (AA+AA) with major alleles of rs76804286 (GG). A case-control association analysis for BMI in obese children (n=51), as compared to normal-weight children (n=162), was based on the effects of genotypes homozygous for the minor alleles of the studied SNPs in recessive and codominant inheritance models (assuming an independent effect of each genotype). A comparison of children with normal BMI with obese children indicate a strong co-dominant effect of a genotype in homozygotes of minor alleles (AA+AA) of completely linked rs9939609+rs9926289 (OR at age 8.89 ± 1.54 years=4.87, 95% CI 1.81-13.12, p=0.002). An almost five-fold increase of obesity risk in the examined children indicates that the genetic factors, associated with excessive body weight gain, exert stronger effects in the early period of ontogenetic development vs. puberty and adulthood. The role of genetic factors in predisposing to obesity declines with age

Bencová D, Siváková D, Luptáková L, Cvícelová M, Michnová A. 2012. Variant in the FTO gene and biomarkers related to health in mature Slovak women. Anthropol Anz 69:189-200.

Cecil J, 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 359:2558-66.

Chang YC, Liu PH, Lee WJ, Chang TJ, Jiang YD, Li HY, et al. 2008. Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 57:2245-52.

Chrzanowska M, Kozieł S, Ulijaszek SJ. 2007. Changes in BMI and the prevalence of overweight and obesity in children and adolescents in Cracow, Poland 1997-2000. Econ Hum Biol 5:370-78.

Chrzanowska M, Suder A. 2010. The extent of overweight index in children and adolescents from Cracow, Poland (1971-2000). HOMO - J Comp Hum Biol 61:453-58.

Chrzanowska M, Łaska-Mierzejewska T, Suder A. 2013. Overweight and obesity in rural girls from Poland: changes between 1987 and 2001. J Biosoc Sci 45:217-29.

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

Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. 2000. Establishing a standard definition for child over-weight and obesity worldwide: international survey. Br Med J 320:1240-43.

Dlouha D, Adamkova V, Lanska V, Hubacek JA. 2010. Lack of association between a new tag SNP in the FTO gene and BMI in Czech-Slavonic population. Eur J Hum Genet 18:1274.

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

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 316:889-94.

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 318:1469-72.

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 doi: 10.1038/ nutd.2012.20.

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

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 53:546-53.

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 2:97-106.

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 - Anthropological Review 68:43-52.

López-Bermejo A, Petry CJ, Díaz M, Sebastiani G, de Zegher F, Dunger DB, et al. 2008. The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinol Metab 93:1501-05.

Luczynski 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 Physiol Pharmacol 63:241-48.

Ohashi J, Naka I, Kimura R, Natsuhara K, Yamauchi T, Furusawa T, et al. 2007. FTO polymorphisms in oceanic populations. J Hum Genet 52:1031-35.

Pan H, Cole TJ. 2011. LMS growth, a Microsoft Excel add-in to access growth references based on the LMS method. Version 2.74. http://www.healthforallchildren.co.uk/.

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 168:1791-97.

Rask-Andersen M, Jacobsson JA, Moschonis G, Chavan RA, Sikder MA, Allzén 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 20:192-97.

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, editor. Dziecko łódzkie 2004. Normy rozwoju biologicznego. Łódź: Wydawnictwo Uniwersytetu Łódzkiego. 39-142.

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) 35:364-72.

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:e115.

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 57:2851-57.

Wahlén K, Sjölin 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 49:607-11.

Wardle J, Carnell S, Haworth CMA. 2008a. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am J Clin Nutr 87:398-404.

Wardle J, Carnell S, Haworth C, Farooqi IS, O’Rahilly S, Plomin R. 2008b. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 93:3640-43.

Wardle J, Llewellyn C, Sanderson S, Plomin R. 2009. The FTO gene and measured food intake in children. Int J Obes Relat Metab Disord 33:42-45.

Wronka I, Suliga E, Pawlińska-Chmara R. 2012. Socioeconomic determinants of underweight and overweight in female Polish students in 2009. Anthropol Anz 69:85-96.

Wronka I. 2013. Socioeconomic status, body mass index and prevalence of underweight and overweight among polish girls aged 7-18: a longitudinal study. J Biosoc Sci. doi: 10.1017/S002193201300031X

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 - J Comp Hum Biol 63:216-32.

Żądzińska E, Rosset I. 2013. Pre-natal and perinatal factors affecting body mass index in pre-pubertal Polish children. Ann Hum Biol 40:477-84.

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CiteScore 2018: 0.55

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