FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men.
FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men.
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DOI：
10.1371/journal.pone.0165523
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tobe K
中科院分区：
文献类型：
--
作者：
Kamura Y;Iwata M;Maeda S;Shinmura S;Koshimizu Y;Honoki H;Fukuda K;Ishiki M;Usui I;Fukushima Y;Takano A;Kato H;Murakami S;Higuchi K;Kobashi C;Tobe K
一些研究表明，脂肪量和肥胖相关基因（FTO）的多态性与2型糖尿病（T2D）有关。然而，FTO基因座对T2D易感性的影响是否独立于脂肪量的增加仍然存在争议。为了研究这一问题，我们在日本人群中研究了FTO变异与T2D和成年期BMI历史各方面的关系。我们对760名在诊断前或诊断时达到一生最大BMI （BMImax）的日本T2D患者和693名具有其BMImax信息的对照个体的FTO内snp （rs1121980和rs1558902）进行了基因分型。在本研究评估的bmi中，BMImax与T2D风险的相关性最强。在性别组合分析中，FTO snp与任何BMI变量或T2D无关，但在性别分层分析中，两种snp都与BMImax显著相关，rs1558902与男性T2D相关。在调整当前BMI和年龄后，SNP与T2D的关联仍然显著，而在调整BMI和年龄后，SNP与T2D的关联不再显著。这些结果表明，FTO多态性对日本男性T2D易感性的影响是通过其在诊断前或诊断时增加BMImax的影响来介导的。
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.
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影响因子：
3.7
作者：
Jacobsson JA;Almén MS;Benedict C;Hedberg LA;Michaëlsson K;Brooks S;Kullberg J;Axelsson T;Johansson L;Ahlström H;Fredriksson R;Lind L;Schiöth HB
通讯作者：
Schiöth HB
影响因子：
8.2
作者：
KADOWAKI, T;MIYAKE, Y;KOSAKA, K
通讯作者：
KOSAKA, K
影响因子：
4.5
作者：
Heard-Costa NL;Zillikens MC;Monda KL;Johansson A;Harris TB;Fu M;Haritunians T;Feitosa MF;Aspelund T;Eiriksdottir G;Garcia M;Launer LJ;Smith AV;Mitchell BD;McArdle PF;Shuldiner AR;Bielinski SJ;Boerwinkle E;Brancati F;Demerath EW;Pankow JS;Arnold AM;Chen YD;Glazer NL;McKnight B;Psaty BM;Rotter JI;Amin N;Campbell H;Gyllensten U;Pattaro C;Pramstaller PP;Rudan I;Struchalin M;Vitart V;Gao X;Kraja A;Province MA;Zhang Q;Atwood LD;Dupuis J;Hirschhorn JN;Jaquish CE;O'Donnell CJ;Vasan RS;White CC;Aulchenko YS;Estrada K;Hofman A;Rivadeneira F;Uitterlinden AG;Witteman JC;Oostra BA;Kaplan RC;Gudnason V;O'Connell JR;Borecki IB;van Duijn CM;Cupples LA;Fox CS;North KE
通讯作者：
North KE
影响因子：
16.2
作者：
Iwata M;Maeda S;Kamura Y;Takano A;Kato H;Murakami S;Higuchi K;Takahashi A;Fujita H;Hara K;Kadowaki T;Tobe K
通讯作者：
Tobe K
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.