Could NCOA5 a novel candidate gene for multiple sclerosis susceptibility?

Mol Biol Rep. 2023 Nov;50(11):9335-9341. doi: 10.1007/s11033-023-08830-6. Epub 2023 Oct 10.

Abstract

Background: Multiple sclerosis (MS) is an inflammatory immune-mediated demyelinating disease that causes a challenging and disabling condition. Environmental and genetic factors play a role in appearing the state of the disease. Recent studies have shown that nuclear cofactor genes may play a role in the pathogenesis of MS. NCOA5 is a nuclear receptor coactivator independent of AF2 that modulates ERa-mediated transcription. This gene is involved in the pathogenesis of diseases such as psoriasis, Behcet's disease, and cancer.

Methods and results: We investigated the relationship between the rs2903908 polymorphism of the NCOA5 gene and MS among 157 unrelated MS patients and 160 healthy controls by RT-PCR. The frequencies of the CC, CT, and TT genotypes were 19.87%, 37.82%, and 42.31%, respectively, for the MS group and 5.63%, 43.75%, and 50.62%, respectively, for the control group. The CC genotype and the C allele were found to be significantly higher in the patient group (the p values were 0.0002 and 0.003, respectively).

Conclusions: The fact that the CC genotype was found to be significantly higher in the patient group compared to the control group (p = 0.0002) and that it had a statistically significantly higher OR value (OR, 95% CI = 4.16, 1.91-9.05) suggests that the C allele may recessively predispose to MS for this polymorphism. These results suggest for the first time that the NCOA5 gene may have an effect on the occurrence of MS through different molecular pathways, which are discussed in the manuscript.

Keywords: Multiple sclerosis; NCOA5; Polymorphisms; Rs2903908; Susceptibility.

MeSH terms

  • Case-Control Studies
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Multiple Sclerosis* / genetics
  • Nuclear Receptor Coactivators / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Transcription Factors / genetics

Substances

  • Transcription Factors
  • NCOA5 protein, human
  • Nuclear Receptor Coactivators