title: Association of Canonical Wnt/β-Catenin Pathway and Type 2 Diabetes: Genetic Epidemiological Study in Han Chinese.
abstract: We aimed to investigate the associations of polymorphisms in Canonical Wnt/β-catenin pathway (WNT) signaling genes (including low-density lipoprotein-related protein 5 [LRP5] and transcription factor 7-like 2 [TCF7L2] gene) and the downstream gene glucagon (GCG) and risk of type 2 diabetes mellitus (T2DM) in a Han Chinese population. We genotyped the single nucleotide polymorphisms (SNPs) for LRP5, TCF7L2 and GCG gene were genotyped in 1842 patients with T2DM and 7777 normal glucose-tolerant healthy subjects. We used multifactor dimensionality reduction (MDR) and multiplicative logistic regression adjusting for sex, age, anthropometric measurements and lipid levels to investigate the gene-gene interactions for the risk of T2DM. Among the five SNPs in LRP5, the recessive model of rs7102273 and the haplotype GCTCC were associated with T2DM risk; the haplotype GCTTC was associated with decreased risk. For TCF7L2, the rs11196218 genotype GA and the haplotype CCG, TTG, TTA were associated with T2DM risk; whereas, the haplotype CTG and TCG were associated with decreased risk. Both MDR and multiplicative logistic regression revealed potential gene-gene interactions among LRP5, TCF7L2, and GCG associated with T2DM. The WNT signaling pathway may play a significant role in risk of T2DM in Han Chinese people.
authors.affiliation: Department of Traditional Chinese Medicine Prevention, Preventive Medicine Research Evaluation Center, Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China. wangjinjin510@yahoo.com.|Department of Epidemiology, Shenzhen University School of Medicine, Shenzhen 518060, China. wangjinjin510@yahoo.com.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Military Hospital of Henan Province, Zhengzhou 450000, China. jingzhi_zhao@sina.com.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Henan Armed Police Corps Hospital, Zhengzhou 450000, China. jeefzhang106@yahoo.com.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, Shenzhen University School of Medicine, Shenzhen 518060, China. lxp2005@szu.edu.cn.
authors.forename: Xinping
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Epidemiology, Shenzhen University School of Medicine, Shenzhen 518060, China. gao_kp@szu.edu.cn.
authors.forename: Kaiping
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Epidemiology, Shenzhen University School of Medicine, Shenzhen 518060, China. zhangming@szu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China. lilinlin@zzu.edu.cn.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China. jwcj2008@zzu.edu.cn.
authors.forename: Chongjian
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Shenzhen University School of Medicine, Shenzhen 518060, China. dongsheng_hu@hotmail.com.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin; D005934:Glucagon
keywords: Chinese; WNT signaling pathway; polymorphisms; type 2 diabetes