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Nutrients 2015, 7(6), 4763-4777; doi:10.3390/nu7064763

Association of Canonical Wnt/β-Catenin Pathway and Type 2 Diabetes: Genetic Epidemiological Study in Han Chinese

1
Department of Traditional Chinese Medicine Prevention, Preventive Medicine Research Evaluation Center, Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China
2
Department of Epidemiology, Shenzhen University School of Medicine, Shenzhen 518060, China
3
Military Hospital of Henan Province, Zhengzhou 450000, China
4
Henan Armed Police Corps Hospital, Zhengzhou 450000, China
5
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 23 March 2015 / Revised: 28 May 2015 / Accepted: 3 June 2015 / Published: 15 June 2015
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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. View Full-Text
Keywords: WNT signaling pathway; polymorphisms; type 2 diabetes; Chinese WNT signaling pathway; polymorphisms; type 2 diabetes; Chinese
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, J.; Zhao, J.; Zhang, J.; Luo, X.; Gao, K.; Zhang, M.; Li, L.; Wang, C.; Hu, D. Association of Canonical Wnt/β-Catenin Pathway and Type 2 Diabetes: Genetic Epidemiological Study in Han Chinese. Nutrients 2015, 7, 4763-4777.

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