ANGPTL8 Gene Polymorphism rs2278426 Is Related to Carotid Intima-Media Thickness in T2DM

Diabetes Metab Syndr Obes. 2020 Nov 20:13:4519-4528. doi: 10.2147/DMSO.S274759. eCollection 2020.

Abstract

Aim: ANGPTL8 is a cytokine expressed and secreted by liver and adipose tissue, and is involved in glucose, lipid, and energy metabolism. Although studies have shown that ANGPTL8 is elevated in type 2 diabetes mellitus (T2DM) and cardiovascular disease, few have examined the association between ANGPTL8 single-nucleotide polymorphisms and the risk of macrovascular complications in T2DM patients. This study aimed to explore the relationship between rs2278426 and carotid intima-media thickening (cIMT) in T2DM.

Methods: A total of 217 T2DM patients and 201 healthy control subjects with normal glucose tolerance were recruited in the study. T2DM patients were divided into two groups: T2DM patients without cIM thickening (cIMT <1 mm, 109 cases) and T2DM patients with cIM thickening (cIMT ≥1 mm, 108 cases). rs2278426 genotypes in all 418 subjects were determined and the risk of T2DM and T2DM with cIM thickening analyzed.

Results: CT+TT-genotype frequency in T2DM was higher than in controls with normal glucose tolerance, and the proportion of the CT+TT genotype in the group with cIMT was higher than in the group (P<0.05). In addition, T alleles were associated with waist:hip ratio, triglycerides, high density-lipoprotein cholesterol, plasma glucose at 2 hours' oral glucose tolerance, and homeostatic model assessment of insulin resistance (P<0.05).

Conclusion: Generally, carriers of the T allele at rs2278426 are more likely to develop T2DM, and the risk of cIM thickening is significantly increased for T-allele carriers with T2DM, which indicates an increased risk of macroangiopathy.

Keywords: angiopoietin‑like protein 8; carotid intima–media thickness; polymorphism; rs2278426; type 2 diabetes mellitus.