Genetic association of MiR-146a with multiple sclerosis susceptibility in the Chinese population

Cell Physiol Biochem. 2015;35(1):281-91. doi: 10.1159/000369695. Epub 2015 Jan 10.

Abstract

Background: miR-146a polymorphisms have been involved in susceptibility to multiple diseases. The aim of the present study was to analyze the potential association between two functional miR-146a polymorphisms (rs2910164 and rs57095329) and multiple sclerosis (MS) in the Han Chinese population.

Methods: A cohort of 525 patients and 568 healthy controls were genotyped to detect the two polymorphisms by SNaPshot.

Results: No significant differences were detected in the distribution of the two miR-146a polymorphisms between the patients and controls (P > 0.05). However, stratification by gender showed a statistically significant difference in the frequency of the genotype rs2910164 between MS patients and control females (P=0.009). Further stratification analysis by subgroup revealed that the miR-146a rs2910164 C allele conferred a higher risk of developing relapsing-remitting MS (RRMS) (P=0.018). In addition, the rs2910164 C allele was significantly associated with increased expression of miR-146a in patients with RRMS (P=0.025). Moreover, patients with the rs2910164 C allele released more TNF-α and IFN-γ, but not IL-1β, compared with individuals carrying the homozygous GG genotype (P < 0.05).

Conclusions: Our results provide evidence that rs2910164 may play a role in MS susceptibility in females. The rs2910164 G>C variation may affect the expression of miR-146a and the release of proinflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • China
  • Cytokines / metabolism
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Homozygote
  • Hospitals
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multiple Sclerosis / classification
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / pathology
  • Polymorphism, Single Nucleotide
  • Sex Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • MIRN146 microRNA, human
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma