Fat Mass and Obesity-associated Gene Rs11642015 Polymorphism is Significantly Associated with Prediabetes and Type 2 Diabetes Subsequent to Adjustment for Body Mass Index

Overview

Journal Biomed Rep

Specialty Biochemistry

Date 2014 Jul 24

PMID 25054011

Citations 3

Authors

Liyuan Han

Linlin Tang

Changyi Wang

Zhongwei Chen

Tao Zhang

Sihan Chen

Shengyuan Liu

XiaoLin Peng

Yifeng Mai

Shiwei Duan

Affiliations

Soon will be listed here.

Abstract

The association of the fat mass and obesity-associated gene () rs11642015 polymorphism with prediabetes, type 2 diabetes and obesity in certain populations has not been previously reported. A population-based study was conducted that included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary logistic regression was performed to estimate the association of rs11642015 with the risk of prediabetes, type 2 diabetes and obesity following adjustment for the corresponding confounders. A meta-analysis was also conducted to evaluate the association between rs11642015 and obesity. rs11642015 was significantly associated with prediabetes in the whole sample under the additive model [odds ratio (OR), 1.50; 95% confidence interval (CI), 1.17-1.93; P=0.002], particularly in females. The polymorphism remained consistently significant following adjustment for age and body mass index (BMI), showing an increased prediabetes risk with an additive effect (OR, 1.55; 95% CI, 1.19-2.01; P=0.001). In addition, a significant association was found for rs11642015 with prediabetes and type 2 diabetes under the dominant model. However, under the stringent Bonferroni's correction there was no evidence of positive associations for rs11642015 with obesity in the whole sample, females or males. Findings of the meta-analysis showed that rs11642015 was not predisposed to obesity. In conclusion, the T allele of rs11642015 is positively associated with an increased risk of prediabetes, even after adjustment for age and BMI, particularly in females. Subjects carrying the CT + TT genotype are predisposed to prediabetes and type 2 diabetes. Therefore, results of the population-based study and follow-up meta-analysis suggested that rs11642015 is not significantly associated with susceptibility to obesity.

Citing Articles

Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations.

Anwar M, Baldassari A, Polikowsky H, Sitlani C, Highland H, Chami N BMC Med Genomics. 2022; 15(1):192.

PMID: 36088317 PMC: 9464371. DOI: 10.1186/s12920-022-01352-3.

Troxerutin protects against diabetic cardiomyopathy through NF‑κB/AKT/IRS1 in a rat model of type 2 diabetes.

Yu Y, Zheng G Mol Med Rep. 2017; 15(6):3473-3478.

PMID: 28440404 PMC: 5436284. DOI: 10.3892/mmr.2017.6456.

FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men.

Kamura Y, Iwata M, Maeda S, Shinmura S, Koshimizu Y, Honoki H PLoS One. 2016; 11(11):e0165523.

PMID: 27820839 PMC: 5098825. DOI: 10.1371/journal.pone.0165523.

References

Zhou B . Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002; 15(1):83-96. View

Adeyemo A, Rotimi C . Genetic variants associated with complex human diseases show wide variation across multiple populations. Public Health Genomics. 2009; 13(2):72-9. PMC: 2835382. DOI: 10.1159/000218711. View

Dupont W, Plummer Jr W . Power and sample size calculations. A review and computer program. Control Clin Trials. 1990; 11(2):116-28. DOI: 10.1016/0197-2456(90)90005-m. View

Binh T, Phuong P, Nhung B, Thoang D, Lien H, Thanh D . Association of the common FTO-rs9939609 polymorphism with type 2 diabetes, independent of obesity-related traits in a Vietnamese population. Gene. 2012; 513(1):31-5. DOI: 10.1016/j.gene.2012.10.082. View

Meyre D . Is FTO a type 2 diabetes susceptibility gene?. Diabetologia. 2012; 55(4):873-6. DOI: 10.1007/s00125-012-2478-4. View

. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010; 33 Suppl 1:S62-9. PMC: 2797383. DOI: 10.2337/dc10-S062. View

Weber M, Oza-Frank R, Staimez L, Ali M, Narayan K . Type 2 diabetes in Asians: prevalence, risk factors, and effectiveness of behavioral intervention at individual and population levels. Annu Rev Nutr. 2012; 32:417-39. DOI: 10.1146/annurev-nutr-071811-150630. View

Hertel J, Johansson S, Sonestedt E, Jonsson A, Lie R, Platou C . FTO, type 2 diabetes, and weight gain throughout adult life: a meta-analysis of 41,504 subjects from the Scandinavian HUNT, MDC, and MPP studies. Diabetes. 2011; 60(5):1637-44. PMC: 3292341. DOI: 10.2337/db10-1340. View

Rovite V, Petrovska R, Vaivade I, Kalnina I, Fridmanis D, Zaharenko L . The role of common and rare MC4R variants and FTO polymorphisms in extreme form of obesity. Mol Biol Rep. 2014; 41(3):1491-500. DOI: 10.1007/s11033-013-2994-4. View

10.

Fazeli Farsani S, van der Aa M, van der Vorst M, Knibbe C, de Boer A . Global trends in the incidence and prevalence of type 2 diabetes in children and adolescents: a systematic review and evaluation of methodological approaches. Diabetologia. 2013; 56(7):1471-88. DOI: 10.1007/s00125-013-2915-z. View

11.

Yajnik C, Janipalli C, Bhaskar S, Kulkarni S, Freathy R, Prakash S . FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia. 2008; 52(2):247-52. PMC: 2658005. DOI: 10.1007/s00125-008-1186-6. View

12.

Kalnina I, Zaharenko L, Vaivade I, Rovite V, Nikitina-Zake L, Peculis R . Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes. Gene. 2013; 527(2):462-8. DOI: 10.1016/j.gene.2013.06.079. View

13.

Cecil J, Dalton M, Finlayson G, Blundell J, Hetherington M, Palmer C . Obesity and eating behaviour in children and adolescents: contribution of common gene polymorphisms. Int Rev Psychiatry. 2012; 24(3):200-10. DOI: 10.3109/09540261.2012.685056. View

14.

Frayling T, Timpson N, Weedon M, Zeggini E, Freathy R, Lindgren C . A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007; 316(5826):889-94. PMC: 2646098. DOI: 10.1126/science.1141634. View

15.

Sallman Almen M, Rask-Andersen M, Jacobsson J, Ameur A, Kalnina I, Moschonis G . Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children. Int J Obes (Lond). 2012; 37(3):424-31. PMC: 3595467. DOI: 10.1038/ijo.2012.57. View

16.

Scott L, Mohlke K, Bonnycastle L, Willer C, Li Y, Duren W . A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007; 316(5829):1341-5. PMC: 3214617. DOI: 10.1126/science.1142382. View

17.

Schmid P, Heid I, Buechler C, Steege A, Resch M, Birner C . Expression of fourteen novel obesity-related genes in Zucker diabetic fatty rats. Cardiovasc Diabetol. 2012; 11:48. PMC: 3398851. DOI: 10.1186/1475-2840-11-48. View

18.

Takeuchi F, Yamamoto K, Katsuya T, Nabika T, Sugiyama T, Fujioka A . Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals. Diabetologia. 2011; 54(6):1350-9. DOI: 10.1007/s00125-011-2086-8. View

19.

Hess M, Bruning J . The fat mass and obesity-associated (FTO) gene: Obesity and beyond?. Biochim Biophys Acta. 2014; 1842(10):2039-47. DOI: 10.1016/j.bbadis.2014.01.017. View

20.

Fredriksson R, Hagglund M, Olszewski P, Stephansson O, Jacobsson J, Olszewska A . 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. 2008; 149(5):2062-71. DOI: 10.1210/en.2007-1457. View