The influence of VDR polymorphisms on the type 2 diabetes susceptibility in Chinese: an interaction with hypertriglyceridemia

Mol Genet Genomics. 2021 Jul;296(4):837-844. doi: 10.1007/s00438-021-01784-z. Epub 2021 Apr 20.

Abstract

Evidence shows that mutations in vitamin D receptor (VDR) have been linked with an increased risk of type 2 diabetes (T2D). However, the interaction effect between VDR variants and environmental factors on the T2D susceptibility remained unclear. Therefore, the current study was conducted to explore the joint effect of VDR polymorphisms and serum triglyceride level on T2D. A total of 2017 participants were included in the cross-sectional study. Taqman probe assays were applied to rs3847987 and rs739837 genotyping. Multiple logistic regression and general linear model were used to examine the effect of interaction between VDR variants and TG on T2D susceptibility and fasting serum glucose, respectively. The results showed that rs739837 polymorphism was significantly associated with an increased risk of T2D under the dominant model (OR = 1.30, 95% CI 1.02-1.66), after adjusting for potential risk factors. Meanwhile, there was a significant additive interaction between rs3847987 and hypertriglyceridemia (synergy index [SI]: 2.98, 95% CI: 1.23-7.23) and between rs739837 and hypertriglyceridemia (SI: 2.36, 95% CI: 1.05-5.31) on T2D susceptibility. Additionally, a significant linear association between fasting glucose and rs3847987 had been found at high triglyceride level (> 1.90 mmol/L) with an inversely concentration-dependent manner. The study provided further evidence that rs739837 and high level of triglyceride were both associated with higher T2D susceptibility in Chinese population. Additionally, the detrimental effect of VDR variants on T2D could be modified by hypertriglyceridemia status.

Keywords: Hypertriglyceridemia; Interaction; Type 2 diabetes; VDR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Asian People / statistics & numerical data
  • China / epidemiology
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / epidemiology
  • Hypertriglyceridemia / genetics*
  • Life Style
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Calcitriol / genetics*
  • Triglycerides / blood

Substances

  • Receptors, Calcitriol
  • Triglycerides
  • VDR protein, human