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.
OBJECTIVE
The objective of the present study was to investigate the genetic association of the fat-mass-and-obesity-associated (FTO) gene in obese women in the presence of the known influential role of the insulin receptor substrate 2 (IRS-2) gene.


METHODS
This case-control study was carried out in the Languedoc-Roussillon region of France, and included lean control women (n=128), and women (n=119) of various degrees of obesity (body mass index [BMI] mean+/-S.D.: 39.3+/-7.4kg/m(2)) and a prevalence of 26.9% of the metabolic syndrome (MetS). For the FTO gene, genotyping was performed by sequence-specific oligonucleotide-polymerase chain reaction (SSO-PCR) on the single nucleotide polymorphism (SNP) rs1421085 (C/T) while, for IRS-2, the rs1805097 (G/A) corresponding to variant Gly1057Asp was genotyped by direct sequencing.


RESULTS
The FTO gene (homozygous C/C) was significantly associated to both simple and morbid obesity (P<0.026 and P<0.0034, respectively), with odds-ratios (ORs) of 2.58 (95% CI: 1.1-6.0) and 4.1 (95% CI: 1.6-10.5), respectively, independent of IRS-2. MetS was also associated with FTO (P<0.032, OR: 3.1, 95% CI: 1.1-8.5), but not with IRS-2. Genotypes of FTO were correlated with insulin resistance, and homozygous C/C was positively correlated with an increase in insulin resistance over the value predicted by the increase in BMI.


CONCLUSIONS
These data confirm the influential role of the FTO gene in obesity in the French female population and, in addition, revealed the role of FTO in insulin resistance and MetS. These effects appeared to be independent of IRS-2, which is directly involved in insulin action. This study may offer new insights into the genetic determinants of obesity and MetS in women.
Attaoua
R
R
IURC, Molecular Endocrinology Laboratory (UMR-204), Montpellier cedex 5, France.
Ait El Mkadem
S
S
Lautier
C
C
Kaouache
S
S
Renard
E
E
Brun
J-F
JF
Fedou
C
C
Gris
J-C
JC
Bringer
J
J
Grigorescu
F
F
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000704:Analysis of Variance; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005602:France; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012044:Regression Analysis
C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human