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: Jinjin Wang, Jingzhi Zhao, Jianfeng Zhang, Xinping Luo, Kaiping Gao, Ming Zhang, Linlin Li, Chongjian Wang, Dongsheng Hu
• Journal: Nutrients (Nutrients) Vol. 7 Issue 6 Pg. 4763-77 (Jun 15 2015) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 26083111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LRP5 protein, human
• Low Density Lipoprotein Receptor-Related Protein-5
• TCF7L2 protein, human
• Transcription Factor 7-Like 2 Protein
• beta Catenin
• Glucagon

Topics

• Adult
• Aged
• Aged, 80 and over
• Alleles
• Asian People (genetics)
• Body Mass Index
• Case-Control Studies
• China
• Diabetes Mellitus, Type 2 (genetics)
• Female
• Genetic Predisposition to Disease
• Genotyping Techniques
• Glucagon (genetics, metabolism)
• Haplotypes
• Humans
• Linkage Disequilibrium
• Logistic Models
• Low Density Lipoprotein Receptor-Related Protein-5 (genetics, metabolism)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Transcription Factor 7-Like 2 Protein (genetics, metabolism)
• Wnt Signaling Pathway
• Young Adult
• beta Catenin (genetics, metabolism)