Skip to main content
Log in

Common variant (rs9939609) in the FTO gene is associated with metabolic syndrome

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Recent genome-wide association studies have showed that common variant (rs9939609) in fat mass and obesity associated (FTO) gene was significantly associated with type 2 diabetes through an effect on human body mass index/obesity. Further studies have suggested that this variant was also involved in the development of metabolic syndrome (MetS). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association between rs9939609 polymorphism and the risk of MetS. Published literature from PubMed, EMBASE and other databases were searched. All studies assessing the association between rs9939609 polymorphism and the risk of MetS were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed-effects model. Thirteen studies (8,370 cases and 23,156 controls) using NCEP ATPIII criteria for MetS were pooled with a meta-analysis. The overall result showed that there was a statistically significant association between rs9939609 polymorphism and MetS risk (OR = 1.11, 95% CI = 1.06–1.17). Subgroup analysis based on ethnicity showed that effect size was only statistically significant in Europeans (OR = 1.11, 95% CI = 1.05–1.16). Eight studies (1,256 cases and 2,551 controls) using IDF criteria for MetS were pooled with a meta-analysis. The overall analysis suggested that rs9939609 polymorphism was significantly associated with MetS risk (OR = 1.32, 95% CI = 1.13–1.54). Subgroup analysis stratified by ethnicity suggested that effect size was only statistically significant in Asians (OR = 1.33, 95% CI = 1.10–1.61). Our results suggested that FTO rs9939609 polymorphism was significantly associated with the increased risk of MetS in European and Asian populations. Mechanistic investigation is also needed to clarify the effect of FTO gene in the predisposition to MetS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bruce KD, Hanson MA (2010) The developmental origins, mechanisms, and implications of metabolic syndrome. J Nutr 140:648–652

    Article  PubMed  CAS  Google Scholar 

  2. Cannon CP (2008) Mixed dyslipidemia, metabolic syndrome, diabetes mellitus, and cardiovascular disease: clinical implications. Am J Cardiol 102:5L–9L

    Article  PubMed  Google Scholar 

  3. Lin HF, Boden-Albala B, Juo SH et al (2005) Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study. Diabetologia 48:2006–2012

    Article  PubMed  Google Scholar 

  4. Frayling TM, Timpson NJ, Weedon MN 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  PubMed  CAS  Google Scholar 

  5. Xi B, Wang C, Wang R et al (2011) FTO gene polymorphisms are associated with obesity and type 2 diabetes in East Asian populations: an update. Obesity (Silver Spring) 19:236–237

    Article  Google Scholar 

  6. Peng S, Zhu Y, Xu F et al (2011) FTO gene polymorphisms and obesity risk: a meta-analysis. BMC Med 8(9):71

    Article  Google Scholar 

  7. Bollepalli S, Dolan LM, Deka R et al (2010) Association of FTO gene variants with adiposity in African-American adolescents. Obesity (Silver Spring) 18:1959–1963

    Article  CAS  Google Scholar 

  8. Ohashi J, Naka I, Kimura R et al (2007) FTO polymorphisms in oceanic populations. J Hum Genet 52:1031–1035

    Article  PubMed  Google Scholar 

  9. Li H, Wu Y, Loos RJ 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  PubMed  CAS  Google Scholar 

  10. Freathy RM, Timpson NJ, Lawlor DA et al (2008) Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes 57:1419–1426

    Article  PubMed  CAS  Google Scholar 

  11. Al-Attar SA, Pollex RL, Ban MR et al (2008) Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample. Cardiovasc Diabetol 7:5

    Article  PubMed  Google Scholar 

  12. Sjögren M, Lyssenko V, Jonsson A et al (2008) The search for putative unifying genetic factors for components of the metabolic syndrome. Diabetologia 51:2242–2251

    Article  PubMed  Google Scholar 

  13. Attaoua R, Ait El Mkadem S, Lautier C et al (2009) Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France. Diabetes Metab 35:476–483

    Article  PubMed  CAS  Google Scholar 

  14. Ranjith N, Pegoraro RJ, Shanmugam R (2011) Obesity-associated genetic variants in young Asian Indians with the metabolic syndrome and myocardial infarction. Cardiovasc J Afr 22:25–30

    Article  PubMed  CAS  Google Scholar 

  15. Sun XQ, Luo YY, Han XR et al (2008) Association of FTO rs9939609 polymorphism and metabolic syndrome in a Chinese Han population. Chin Med J 121:243 (in Chinese)

    Google Scholar 

  16. Wang T, Huang Y, Xiao XH et al (2010) The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese. Chin Med J (Engl) 123:1852–1858

    CAS  Google Scholar 

  17. Wan QQ, Zhou B, Fan J et al (2010) Effect of interactions between FTO gene variation and lifestyle on metabolic syndrome. Med J Chin PLA 35:513–516 (in Chinese)

    CAS  Google Scholar 

  18. Cruz M, Valladares-Salgado A, Garcia-Mena J et al (2010) Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City. Diabetes Metab Res Rev 26:261–270

    Article  PubMed  CAS  Google Scholar 

  19. Xu ZY, Song JY, Wang HJ et al. (2011) Study on relationship between MC4R, FTO gene polymorphisms and metabolic syndrome-related phenotypes. Sciencepaper Online http://www.paper.edu.cn (in Chinese)

  20. Cheung CY, Tso AW, Cheung BM et al (2011) Genetic variants associated with persistent central obesity and the metabolic syndrome in a 12-year longitudinal study. Eur J Endocrinol 164:381–388

    Article  PubMed  CAS  Google Scholar 

  21. Shimaoka I, Kamide K, Ohishi M et al (2010) Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese. Hypertens Res 33:214–218

    Article  PubMed  CAS  Google Scholar 

  22. Liem ET, Vonk JM, Sauer PJ et al (2010) Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: the TRAILS (Tracking Adolescents’ Individual Lives Survey) Study. Am J Clin Nutr 91:321–328

    Article  PubMed  CAS  Google Scholar 

  23. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  24. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  PubMed  CAS  Google Scholar 

  25. Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  26. Ford ES, Giles WH, Dietz WH (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359

    Article  PubMed  Google Scholar 

  27. Daskalopoulou SS, Athyros VG, Kolovou GD et al (2006) Definitions of metabolic syndrome: where are we now? Curr Vasc Pharmacol 4:185–197

    Article  PubMed  CAS  Google Scholar 

  28. Willer CJ, Speliotes EK, Loos RJ et al (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41:25–34

    Article  PubMed  CAS  Google Scholar 

  29. Speakman JR, Rance KA, Johnstone AM (2008) Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (SilverSpring) 16:1961–1965

    Article  CAS  Google Scholar 

  30. Tanofsky-Kraff M, Han JC, Anandalingam K et al (2009) The FTO gene rs9939609 obesity-risk allele and loss of control overeating. Am J Clin Nutr 90:1483–1488

    Article  PubMed  CAS  Google Scholar 

  31. Cecil JE, Tavendale R, Watt P et al (2008) An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 359:2558–2566

    Article  PubMed  CAS  Google Scholar 

  32. Larder R, Cheung MK, Tung YC et al (2011) Where to go with FTO? Trends Endocrinol Metab 22:53–59

    Article  PubMed  CAS  Google Scholar 

  33. Guyenet PG (2006) The sympathetic control of blood pressure. Nat Rev Neurosci 7:335–346

    Article  PubMed  CAS  Google Scholar 

  34. Pausova Z, Syme C, Abrahamowicz M et al (2009) A common variant of the FTO gene is associated with not only increased adiposity but also elevated blood pressure in French Canadians. Circulation 2:260–269

    PubMed  CAS  Google Scholar 

  35. Alberti KG, Eckel RH, Grundy SM et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the study of obesity. Circulation 120:1640–1645

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Lin Liao or Fang He.

Additional information

Donghao Zhou and Hongjun Liu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, D., Liu, H., Zhou, M. et al. Common variant (rs9939609) in the FTO gene is associated with metabolic syndrome. Mol Biol Rep 39, 6555–6561 (2012). https://doi.org/10.1007/s11033-012-1484-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1484-4

Keywords

Navigation