title: The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population.
abstract: 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 [P(sign)] = 0.025; P value from permutation test [P(perm)] = 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.
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. lilin.gong@outlook.com.
authors.forename: Lilin
authors.identifier: http://orcid.org/0000-0003-4110-1935
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Rong
authors.identifier: http://orcid.org/0000-0001-6365-5782
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.identifier: http://orcid.org/0000-0003-4222-8217
authors.initials: W
authors.lastname: Ren
authors.affiliation: Laboratory for Disease and Gene, Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Department of Public Health, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zengchan
authors.identifier: http://orcid.org/0000-0002-0525-5315
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhihong
authors.identifier: http://orcid.org/0000-0002-8259-9947
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory for Disease and Gene, Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Department of Public Health, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Laboratory of Disorders Genes and Department of Pharmacology, Jishou University, Jishou, China.
authors.forename: Maosheng
authors.identifier: http://orcid.org/0000-0003-3059-4690
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Suhua
authors.identifier: http://orcid.org/0000-0003-2033-473X
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D000071161:Forkhead Box Protein O1; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins
keywords: FOXO1; Gene and Environment; IRS2; Obesity; Type 2 Diabetes