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Association of a common rs9939609 variant in the fat mass and obesity-associated (FTO) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study

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Abstract

It is a key challenge to conduct reproducibility in genetic research, especially association studies in obesity. While susceptibility of a single-nucleotide polymorphism (SNP), rs9939609, in the fat mass and obesity-associated (FTO) gene to obesity has been reported in various populations, data from Asians is less conclusive. This replication study was carried out to test whether the FTO rs9939609 SNP is a predictive factor for obesity and obesity-related metabolic traits in a Taiwanese population. A total of 1188 Taiwanese subjects were recruited for this study. The FTO rs9939609 SNP was genotyped by the Taqman assay. Obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase and fasting glucose were measured. Our data revealed that the FTOrs9939609 SNP exhibited a significant association with obesity (BMI \(\geqq \) 30 kg/m 2) among the subjects (P= 0.026). However, the FTO rs9939609 SNP did not exhibit any significant association with obesity-related metabolic traits among the subjects. Our results indicated that the FTO rs9939609 SNP may be linked with the risk of obesity in Taiwanese subjects.

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References

  • Andreasen C. H., Stender-Petersen K. L., Mogensen M. S., Torekov S. S., Wegner L., Andersen G. et al. 2008 Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57, 95–101.

    Article  CAS  PubMed  Google Scholar 

  • Bray G. A. and Bellanger T. 2006 Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. Endocrine 29, 109–117.

    Article  CAS  PubMed  Google Scholar 

  • Chang Y. C., Liu P. H., Lee W. J., Chang T. J., Jiang Y. D., Li H. Y. 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, 2245–2252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Day F. R. and Loos R. J. 2011 Developments in obesity genetics in the era of genome-wide association studies. J. Nutrigenet. Nutrigenomics 4, 222–238.

    Article  PubMed  Google Scholar 

  • Erbey J. R., Silberman C. and Lydick E. 2000 Prevalence of abnormal serum alanine aminotransferase levels in obese patients and patients with type 2 diabetes. Am. J. Med. 109, 588–590.

    Article  CAS  PubMed  Google Scholar 

  • Frayling T. M., Timpson N. J., Weedon M. N., Zeggini E., Freathy R. M., Lindgren C. M. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fredriksson R., Hagglund M., Olszewski P. K., Stephansson O., Jacobsson J. A., Olszewska A. M. et al. 2008 The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 149, 2062–2071.

    Article  CAS  PubMed  Google Scholar 

  • Fu T., Wen T., Yeh P. and Chang H. 2008 Costs of metabolic syndrome-related diseases induced by obesity in Taiwan. Obes. Rev. 9 suppl 1, 68–73.

    Article  PubMed  Google Scholar 

  • Gerken T., Girard C. A., Tung Y. C., Webby C. J., Saudek V., Hewitson K. S. et al. 2007 The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318, 1469–1472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grundy S. M. 2004 Obesity, metabolic syndrome, and cardiovascular disease. J. Clin. Endocrinol. Metab. 89, 2595–2600.

    Article  CAS  PubMed  Google Scholar 

  • Hinney A., Nguyen T. T., Scherag A., Friedel S., Brönner G., Müller T. D. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hinney A., Vogel C. I. and Hebebrand J. 2010 From monogenic to polygenic obesity: recent advances. Eur. Child Adolesc. Psychiat. 19, 297–310.

    Article  Google Scholar 

  • Horikoshi M., Hara K., Ito C., Shojima N., Nagai R., Ueki K. et al. 2007 Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia 50, 2461–2466.

    Article  CAS  PubMed  Google Scholar 

  • Hossain P. 2007 Obesity and diabetes in the developing world—a growing challenge. N. Engl. J. Med. 356, 973.

    Article  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, 546–553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsiao T. J., Hwang Y., Chang H. M. and Lin E. 2014 Association of the rs6235 variant in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene with obesity and related traits in a Taiwanese population. Gene 533, 32–37.

    Article  CAS  PubMed  Google Scholar 

  • Hsiao T. J., Hwang Y., Liu C. H., Chang H. M. and Lin E. 2013 Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population. Genes Nutr. 8, 137–144.

    Article  CAS  PubMed  Google Scholar 

  • Hsiao T. J. and Lin E. 2014 Evaluation of the glutamine 27 glutamic acid polymorphism in the adrenoceptor beta 2 surface gene on obesity and metabolic phenotypes in Taiwan. J. Investig. Med. 62, 310–315.

    Article  CAS  PubMed  Google Scholar 

  • Hsiao T. J. and Lin E. 2015 The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma (PPARG) gene in relation to obesity and metabolic phenotypes in a Taiwanese population. Endocrine 48, 786–793.

    Article  CAS  PubMed  Google Scholar 

  • Hsiao D. J., Wu L. S., Huang S. Y. and Lin E. 2009 Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet. Genomics 19, 730–733.

    Article  CAS  PubMed  Google Scholar 

  • Karasawa S., Daimon M., Sasaki S., Toriyama S., Oizumi T., Susa S. et al. 2010 Association of the common fat mass and obesity associated (FTO) gene polymorphism with obesity in a Japanese population. Endocr. J. 57, 293–301.

    Article  CAS  PubMed  Google Scholar 

  • Kelly T., Yang W., Chen C. S., Reynolds K. and He J. 2008 Global burden of obesity in 2005 and projections to 2030. Int. J. Obes. (London) 32, 1431–1437.

    Article  CAS  Google Scholar 

  • Lane H. Y., Tsai G. E. and Lin E. 2012 Assessing gene–gene interactions in pharmacogenomics. Mol. Diagn. Ther. 16, 15–27.

    Article  CAS  PubMed  Google Scholar 

  • Legry V., Cottel D., Ferrieres J., Arveiler D., Andrieux N., Bingham A. et al. 2009 Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus in the French MONICA Study. Metabolism 58, 971–975.

    Article  CAS  PubMed  Google Scholar 

  • Li A. and Meyre D. 2013 Challenges in reproducibility of genetic association studies: lessons learned from the obesity field. Int. J. Obes. (London) 37, 559–567.

    Article  CAS  Google Scholar 

  • Li H., Kilpeläinen T. O., Liu C., Zhu J., Liu Y., Hu C. et al. 2012 Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. Diabetologia 55, 981–995.

    Article  CAS  PubMed  Google Scholar 

  • Li H., Wu Y., Loos R. J., Hu F. B., Liu Y., Wang J. et al. 2008 Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes 57, 264–268.

    Article  CAS  PubMed  Google Scholar 

  • Li X., Song F., Jiang H., Zhang M., Lin J., Bao W. et al. 2010 A genetic variation in the fat mass- and obesity-associated gene is associated with obesity and newly diagnosed type 2 diabetes in a Chinese population. Diabetes Metab. Res. Rev. 26, 128–132.

    Article  CAS  PubMed  Google Scholar 

  • Lin E., Pei D., Huang Y. J., Hsieh C. H. and Wu L. S. 2009 Gene–gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes. Genet. Test Mol. Biomarkers 13, 485–493.

    Article  CAS  PubMed  Google Scholar 

  • Liou Y. J., Bai Y. M., Lin E., Chen J. Y., Chen T. T., Hong C. J. et al. 2012 Gene–gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. Pharmacogenomics J. 12, 54–61.

    Article  CAS  PubMed  Google Scholar 

  • Liu Y., Liu Z., Song Y., Zhou D., Zhang D., Zhao T. et al. 2010 Meta-analysis added power to identify variants in FTO associated with type 2 diabetes and obesity in the Asian population. Obesity (Silver Spring) 18, 1619–1624.

    Article  CAS  Google Scholar 

  • Marvelle A. F., Lange L. A., Qin L., Adair L. S. and Mohlke K. L. 2008 Association of FTO with obesity-related traits in the Cebu longitudinal health and nutrition survey (CLHNS) cohort. Diabetes 57, 1987–1991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogden C. L., Yanovski S. Z., Carroll M. D. and Flegal K. M. 2007 The epidemiology of obesity. Gastroenterology 132, 2087–2102.

    Article  PubMed  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, 1031–1035.

    Article  PubMed  Google Scholar 

  • Peeters A., Beckers S., Verrijken A., Roevens P., Peeters P., Van Gaal L. et al. 2008 Variants in the FTO gene are associated with common obesity in the Belgian population. Mol. Genet. Metab. 93, 481–484.

    Article  CAS  PubMed  Google Scholar 

  • Price R. A., Li W. D. and Zhao H. Y. 2008 FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs. BMC Med. Genet. 9, 4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rauhio A., Uusi-Rasi K., Nikkari S. T., Kannus P., Sievänen H. and Kunnas T. 2013 Association of the FTO and ADRB2 genes with body composition and fat distribution in obese women. Maturitas 76, 165–171.

    Article  CAS  PubMed  Google Scholar 

  • Scuteri A., Sanna S., Chen W. M., 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, 1200–1210.

    Article  CAS  Google Scholar 

  • Song Y., You N. C., Hsu Y. H., Howard B. V., Langer R. D., Manson J. E. et al. 2008 FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. Obesity (Silver Spring) 16, 2472–2480.

    Article  CAS  PubMed Central  Google Scholar 

  • Tabara Y., Osawa H., Guo H., Kawamoto R., Onuma H., Shimizu I. et al. 2009 Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study. Int. J. Obes. (London) 33, 1243–1248.

    Article  CAS  Google Scholar 

  • Tan J. T., Dorajoo R., Seielstad M., Sim X. L., Ong R. T., Chia K. S. et al. 2008 FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 57, 2851–2857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wahlen K., Sjolin E. and 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, 607–611.

    Article  PubMed  Google Scholar 

  • Wu L. S., Hsieh C. H., Pei D., Hung Y. J., Kuo S. W. and Lin E. 2009 Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol. Dial. Transplant. 24, 3360–3366.

    Article  CAS  PubMed  Google Scholar 

  • Yajnik C. S., Janipalli C. S., Bhaskar S., Kulkarni S. R., Freathy R. M., Prakash S. et al. 2009 FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia 52, 247–252.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We extend our sincere thanks to Vita Genomics Inc. and SBIR grants from the Department of Economic Affairs in Taiwan for funding this research. We would also like to thank Dr Hua-Mei Chang of Vita Genomics, Dr Yuchi Hwang of Vita Genomics, Dr Dee Pei of the Cardinal Tien Hospital, Dr Yi-Jen Hung of the Tri-Service General Hospital and Dr Shi-Wen Kuo of the Buddhist Xindian Tzu Chi General Hospital for research collaboration.

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Authors and Affiliations

  1. College of Public Health and Nutrition, Taipei Medical University, Taipei, 11031, Taiwan

    TUN-JEN HSIAO

  2. Vita Genomics, Inc., 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, 24872, Taiwan

    EUGENE LIN

  3. Institute of Clinical Medical Science, China Medical University, Taichung, 40402, Taiwan

    EUGENE LIN

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  1. TUN-JEN HSIAO
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Correspondence to EUGENE LIN.

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[Hsiao T.-J. and Lin E. 2016 Association of a common rs9939609 variant in the fat mass and obesity-associated (FTO) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study. J. Genet. 95, xx–xx]

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HSIAO, TJ., LIN, E. Association of a common rs9939609 variant in the fat mass and obesity-associated (FTO) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study. J Genet 95, 595–601 (2016). https://doi.org/10.1007/s12041-016-0671-9

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