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Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study

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Abstract

Multiple studies have identified FTO gene variants associated with measures of adiposity in European-derived populations. The objective of the study was to determine whether FTO variants were associated with adiposity, including visceral and subcutaneous adipose tissue (VAT, SAT), and glucose homeostasis measures in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A total of 27 SNPs in FTO intron 1, including SNPs prominent in the literature (rs9939609, rs8050136, rs1121980, rs17817449, rs1421085, and rs3751812), were genotyped in 1,424 Hispanic Americans and 604 African Americans. Multiple SNPs were associated with BMI and SAT (P values ranging from 0.001 to 0.033), and trending or associated with waist circumference (P values ranging from 0.008 to 0.099) in the Hispanic Americans. No association was observed with VAT, illustrating that FTO variants are associated with overall fat mass instead of specific fat depots. For the glucose homeostasis measures, variants were associated with fasting insulin but, consistent with other studies, after BMI adjustment, no evidence of association remained. The lack of association of FTO SNPs with insulin sensitivity is consistent with the lack of association with VAT, since these traits are strongly correlated. In the African Americans, only rs8050136 and rs9939609 were associated with BMI and WAIST (P values of 0.011 and 0.034), and associated or trending towards association with SAT (P values of 0.038 and 0.058). These results confirm that FTO variants are associated with adiposity measures, predisposing individuals to obesity by increasing overall fat mass in Hispanic Americans and to a lesser degree in African Americans.

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Acknowledgments

This research was supported in part by NIH grants HL060894, HL060931, HL060944, HL061019, and HL061210. We acknowledge the support of the Wake Forest University Health Sciences Center for Public Health Genomics.

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Authors and Affiliations

  1. Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    Maria R. Wing & Donald W. Bowden

  2. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Maria R. Wing, Maggie C. Y. Ng & Donald W. Bowden

  3. Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Julie Ziegler & Carl D. Langefeld

  4. Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Donald W. Bowden

  5. Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA

    Steven M. Haffner

  6. Department of Epidemiology, University of Colorado Denver, Denver, CO, USA

    Jill M. Norris

  7. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Mark O. Goodarzi

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  1. Maria R. Wing
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Correspondence to Donald W. Bowden.

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Wing, M.R., Ziegler, J., Langefeld, C.D. et al. Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study. Hum Genet 125, 615–626 (2009). https://doi.org/10.1007/s00439-009-0656-3

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