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.