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

Hum Genet. 2009 Jun;125(5-6):615-26. doi: 10.1007/s00439-009-0656-3. Epub 2009 Mar 26.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics
  • Adult
  • African Americans / genetics
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Blood Glucose / genetics*
  • Body Mass Index
  • Female
  • Genotype
  • Hispanic Americans / genetics
  • Homeostasis*
  • Humans
  • Intra-Abdominal Fat / metabolism
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • Subcutaneous Fat / metabolism
  • Waist Circumference

Substances

  • Blood Glucose
  • Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Grant support