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

Several studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population.We genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMImax) before or at the time of diagnosis and 693 control individuals with information regarding their BMImax.The BMImax showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMImax and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMImax and age.These results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMImax before or at the time of diagnosis

Association of 2 SNPs with current and lifetime maximum BMI in control and case subjects.

<p>Association of 2 SNPs with current and lifetime maximum BMI in control and case subjects.</p

Genotype, allele frequencies, and HWE of 2SNPs within <i>FTO</i> gene in the present population.

<p>Genotype, allele frequencies, and HWE of 2SNPs within <i>FTO</i> gene in the present population.</p

Clinical characteristics of the study subjects.

<p>Clinical characteristics of the study subjects.</p

Comparison of the serum total adiponectin level between diabetic subjects treated with and without pioglitazone.

<p>Comparison of the serum total adiponectin level between diabetic subjects treated with and without pioglitazone.</p

Comparison of the various adiponectin-related parameters between diabetic subjects and control subjects in the 1^st group.

<p>Comparison of the various adiponectin-related parameters between diabetic subjects and control subjects in the 1^st group.</p

Association results between 2 SNPs and type 2 diabetes.

<p>Association results between 2 SNPs and type 2 diabetes.</p

Association of the various aspects of BMI history with type 2 diabetes.

<p>Association of the various aspects of BMI history with type 2 diabetes.</p

Odds ratios of adiponectin-related parameters for diabetes in the 1^st group.

<p>Odds ratios of adiponectin-related parameters for diabetes in the 1^st group.</p