The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population.
The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population.
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DOI：
10.3346/jkms.2017.32.2.264
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发表时间：
2017-02
影响因子：
4.5
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Gong L;Li R;Ren W;Wang Z;Wang Z;Yang M;Zhang S
在这里，我们旨在研究叉头盒O1-胰岛素受体底物2(FOXO1-IRS2)基因相互作用以及FOXO1和IRS2基因与环境相互作用对中国汉族人群2型糖尿病(T2 DM)风险的影响。对780例无血缘关系的中国汉族人群(474例T2 DM和306例健康对照)的FOXO1基因和IRS2基因的7个多态位点进行了基因分型。FoxO1基因Rs7986407 AA型和Rs4581585 CC型个体患T2 DM的风险分别是GG型(优势比[OR]=2.092；95%可信区间[CI]=1.178~3.731；P=0.011)和TT型(OR=2.571；95%CI=1.404~4.695；P=0.002)的2.092倍和2.57倍。IRS2基因Gly1057Asp携带者患T2 DM的风险是AA携带者的1.42倍(OR=1.422；95%CI=1.037~1.949；P=0.029)。其他4个单核苷酸多态(SNPs)与T2 DM无显著关联(P>；0.05)。多因素降维(MDR)分析表明，FOXO1基因rs7986407和rs4325426与腰围的互作模型最好，与T2 DM密切相关。非肥胖者合并AA/CC、AA/AC或AG/AA基因rs7986407和rs4325426，肥胖者合并rs7986407或rs4325426 AA(OR=3.976；95%CI=1.156~13.675；符号检验P值=0.025；置换检验P值[Pperm]=0.000~0.001)。综上所述，本研究表明FOXO1和IRS2基因多态性与中国汉族人群T2 DM存在关联，支持FOXO1与肥胖的交互作用是T2 DM风险的关键因素。
Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178–3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404–4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037–1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156–13.675; P value from sign test [Psign] = 0.025; P value from permutation test [Pperm] = 0.000–0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.
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