Interactions of TRAF6 and NLRX1 gene polymorphisms with environmental factors on the susceptibility of type 2 diabetes mellitus vascular complications in a southern Han Chinese population

J Diabetes Complications. 2017 Dec;31(12):1652-1657. doi: 10.1016/j.jdiacomp.2017.08.013. Epub 2017 Sep 1.

Abstract

Aims: To evaluate the effects of TRAF6 and NLRX1 polymorphisms and their interactions with environmental factors on the susceptibility of type 2 diabetes mellitus (T2DM) vascular complications in a southern Han Chinese population.

Methods: Five single nucleotide polymorphisms (SNPs) were genotyped in a case-control study to estimate risk factors of T2DM vascular complications. Gene-gene and gene-environment interactions and haplotype associations were also estimated.

Results: The CA genotype of the NLRX1 rs4245191 was identified as a risk factor for T2DM macrovascular complications and diabetic cerebral infarction (OR=2.88, 95% CI=1.15-7.22, P=0.024; OR=4.00, 95% CI=1.04-15.38, P=0.043, respectively). A significantly lower T allele frequency in the TRAF6 rs16928973 was observed in T2DM patients with both microvascular and macrovascular complications compared with patients without any complication under the allelic model (T vs. C: OR=0.36, 95% CI=0.14-0.98, P=0.038). No significant differences in haplotypes, gene-gene interactions and gene-environment interactions were observed among T2DM vascular subgroup patients.

Conclusions: Our study provides evidence that the NLRX1 rs4245191 polymorphisms influence the risk of T2DM macrovascular complications and diabetic cerebral infarction.

Keywords: Complication; Genetics; Interaction; NLRX1; T2DM; TRAF6.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People
  • Case-Control Studies
  • Cerebral Infarction / complications
  • Cerebral Infarction / genetics
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / physiopathology
  • China
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Angiopathies / genetics*
  • Diabetic Angiopathies / metabolism
  • Diabetic Angiopathies / physiopathology
  • Female
  • Gene Frequency
  • Gene-Environment Interaction*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Microvessels / physiopathology
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Polymorphism, Single Nucleotide*
  • Severity of Illness Index
  • TNF Receptor-Associated Factor 6 / genetics*
  • TNF Receptor-Associated Factor 6 / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • NLRX1 protein, human
  • TNF Receptor-Associated Factor 6
  • Tifab protein, human