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PLoS One. 2016 Nov 7;11(11):e0165523. doi: 10.1371/journal.pone.0165523. eCollection 2016.

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

Author information

1
First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan.
2
Health Administration Center, University of Toyama, Toyama, Japan.
3
Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Kanagawa, Japan.
4
Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
5
Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Okinawa, Japan.
6
Department of Internal Medicine, Asahi General Hospital, Asahi-machi, Toyama, Japan.
7
Division of Endocrinology and Metabolism, Department of Internal Medicine, Saiseikai Takaoka Hospital, Takaoka, Toyama, Japan.
8
Division of Endocrinology and Metabolism, Department of Internal Medicine, Japan Community Health care Organization Takaoka Fushiki Hospital, Takaoka, Toyama, Japan.
9
Division of Endocrinology and Metabolism, Department of Internal Medicine, Toyama Rosai Hospital, Uozu, Toyama, Japan.
10
Department of Internal Medicine, Kouseiren Itoigawa General Hospital, Itoigawa, Niigata, Japan.
11
Department of Internal Medicine, Kamiichi General Hospital, Kamiichi-machi, Toyama, Japan.

Abstract

AIM:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
27820839
PMCID:
PMC5098825
DOI:
10.1371/journal.pone.0165523
[Indexed for MEDLINE]
Free PMC Article

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