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PMID: 21102551 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Analysis of FTO gene variants with obesity and glucose homeostasis measures in the multiethnic Insulin Resistance Atherosclerosis Study cohort.

International journal of obesity (2005) ·Vol. 35 ·No. 9 ·2011-09-00 ·Pages 1173-82

Wing MR, Ziegler JM, Langefeld CD, Roh BH, Palmer ND, Mayer-Davis EJ, Rewers MJ, Haffner SM, Wagenknecht LE, Bowden DW

Abstract

Previous studies have replicated the association of variants within FTO (fat mass- and obesity-associated) intron 1 with obesity and adiposity quantitative traits in populations of European ancestry. Non-European populations, however, have not been so intensively studied. The goal of this investigation was to examine the association of FTO single-nucleotide polymorphisms (SNPs), prominent in the literature in a multiethnic sample of non-Hispanic White American (n=458), Hispanic American (n=373) and African American (n=288) subjects from the Insulin Resistance Atherosclerosis Study (IRAS). This cohort provides the unique ability to evaluate how variation within FTO influences measures of adiposity and glucose homeostasis in three different ethnicities, which were ascertained and examined using a common protocol. A total of 26 FTO SNPs were genotyped, including those consistently associated in the literature (rs9939609, rs8050136, rs1121980, rs1421085, rs17817449 and rs3751812), and tested for association with adiposity and glucose homeostasis traits. For the adiposity phenotypes, these and other SNPs were associated with body mass index (BMI) in both non-Hispanic Whites (P-values ranging from 0.015 to 0.048) and Hispanic Americans (P-values ranging from 7.1 × 10(-6) to 0.027). In Hispanic Americans, four other SNPs (rs8047395, rs10852521, rs8057044 and rs8044769) still showed evidence of association after multiple comparisons adjustment (P-values ranging from 5.0 × 10(-5) to 5.2 × 10(-4)). The historically associated BMI SNPs were not associated in the African Americans, but rs1108102 was associated with BMI (P-value of 5.4 × 10(-4)) after accounting for multiple comparisons. For glucose homeostasis traits, associations were seen with acute insulin response in non-Hispanic Whites and African Americans. However, all associations with glucose homeostasis measures were no longer significant after adjusting for multiple comparisons. These results replicate the association of FTO intron 1 variants with BMI in non-Hispanic Whites and Hispanic Americans but show little evidence of association in African Americans, suggesting that the effect of FTO variants on adiposity phenotypes shows genetic heterogeneity dependent on ethnicity.

MeSH Terms
Adiposity/ethnology,genetics Adult African Americans/genetics Aged Atherosclerosis/ethnology,genetics Blood Glucose/metabolism Body Mass Index Female Genetic Predisposition to Disease Genotype Hispanic or Latino/ethnology,genetics Homeostasis Humans Insulin Resistance/ethnology,genetics Male Middle Aged Obesity/blood,ethnology,genetics Polymorphism, Single Nucleotide Whites/genetics
Chemicals
Blood Glucose
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Wing M R
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Ziegler J M
Langefeld C D
Roh B H
Palmer N D
Mayer-Davis E J
Rewers M J
Haffner S M
Wagenknecht L E
Bowden D W
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Article Info
Journal
International journal of obesity (2005)
Abbr.
Int J Obes (Lond)
ISSN
1476-5497
DOI
10.1038/ijo.2010.244
Published
2011-09-00
Epub
2010-00-23
Pages
1173-82
Language
English
Region
England
NLM ID
101256108
PMCID
PMC4068260
Subset
IM
Grants
NHLBI NIH HHS · R01 HL061210 · United States
NHLBI NIH HHS · HL061210 · United States
NHLBI NIH HHS · R01 HL060944 · United States
NHLBI NIH HHS · R01 HL061019 · United States
NHLBI NIH HHS · HL060944 · United States
NHLBI NIH HHS · R01 HL060931 · United States
NHLBI NIH HHS · HL061019 · United States
NHLBI NIH HHS · R01 HL060894 · United States
NHLBI NIH HHS · HL060894 · United States
NHLBI NIH HHS · HL060931 · United States
External Links
PubMed source DOI: 10.1038/ijo.2010.244 PMC Full Text View journal details
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