Association of LRP5, TCF7L2, and GCG variants and type 2 diabetes mellitus as well as fasting plasma glucose and lipid metabolism indexes

Abstract

Recent data puts WNT signaling pathway in a pivotal role in regulating pancreas development as well as islet function, insulin production and secretion. The key effectors in the WNT signaling pathway are low-density lipoprotein receptor-related protein 5 (LRP5), transcription factor 7-like 2 (TCF7L2), and downstream-regulated glucagon (GCG). Our previous studies suggest that the WNT signaling pathway plays a significant role in risk of type 2 diabetes mellitus (T2DM) in Chinese population. The main purpose of the present study was to investigate the associations of single nucleotide polymorphisms (SNPs) in LRP5, TCF7L2 and glucagon (GCG) and quantitative traits in a healthy population. We used tag SNP to screen candidate SNPs for LRP5 and GCG; for TCF7L2, used the confirmed SNP rs11196218. A total of 1842 patients with T2DM and 7777 healthy controls underwent genotyping for the SNPs. We found a significant association of rs3758644 in LRP5 and fasting plasma glucose (p=0.006), and rs11196218 in TCF7L2 and triglycerides level (p=0.004). Among the SNPs in LRP5, TCF7L2, and GCG analyzed, only rs3758644 of LRP5 and rs11196218 of TCF7L2 were significantly associated with fasting plasma glucose and triglycerides index, respectively, in a healthy population.

Keywords: Fasting plasma glucose; GCG; LRP5; TCF7L2.