Association between rs2278426 (C/T) and rs892066 (C/G) variants of ANGPTL8 (betatrophin) and susceptibility to type2 diabetes mellitus.

Abstract

Angiopoietin-like protein 8 (ANGPTL8) is a hormone that mainly secreted from the liver and adipose tissue and plays an important role in the proliferation of pancreatic beta cells and lipid metabolism. Therefore, we studied the association of ANGPTL8 rs2278426 (C/T) and rs892066 (C/G) polymorphisms with the risk of type 2 diabetes mellitus (T2DM) and their association with biochemical parameters. Two hundred and eighty-eight subjects (controls; n=138 and type 2 diabetic patients; n=150) were enrolled in this study. Direct haplotyping was performed using amplification-refractory mutation system (ARMS)-RFLP-PCR. The CT genotype frequency of rs2278426 (C/T) variant was significantly higher in T2DM patients compared to the controls group (P=0.02), and there was a significant association between this genotype and increased risk of T2DM (OR: 2.41, CI: 1.26-4.59, P=0.007). In addition, there was a significant relationship between CT genotype of this variant and high-density lipoprotein cholesterol (HDL-C), fasting blood sugar (FBS), insulin, insulin resistance and glycated hemoglobin (P<0.05). Furthermore, bioinformatics analysis revealed that arginine (Arg) to tryptophan (Trp) substitution at rs2278426 position causes structural instability of ANGPTL8 protein. Genotype and allele distribution of rs892066 (C/G) was not statistically significant in T2DM patients compared to the control group. The distribution of haplotypes had no significant difference between controls and T2DM patients (P=0.24). Our results suggest that the rs2278426 (C/T) variant is associated with increased risk of T2DM and may cause dyslipidemia due to its effect on decreasing HDL-C levels.