Association of SNPs of CD40 gene with multiple sclerosis in Russians

PLoS One. 2013 Apr 22;8(4):e61032. doi: 10.1371/journal.pone.0061032. Print 2013.


Multiple sclerosis (MS) is a serious, incurable neurological disease. In 2009, the ANZgene studies detected the suggestive association of located upstream of CD40 gene in chromosome 20q13 (p = 1.3×10(-7)). Identification of the causal variant(s) in the CD40 locus leads to a better understanding of the mechanism underlying the development of autoimmune pathologies. We determined the genotypes of rs6074022, rs1883832, rs1535045, and rs11086996 in patients with MS (n = 1684) and in the control group (n = 879). Two SNPs were significantly associated with MS: rs6074022 (additive model C allele OR = 1.27, 95% CI = [1.12-1.45], p = 3×10(-4)) and rs1883832 (additive model T allele OR = 1.20, 95% CI = [1.05-1.38], p = 7×10(-3)). In the meta-analysis of our results and the results of four previous studies, we obtain the association p-value of 2.34×10(-12), which confirmed the association between MS and rs6074022 at a genome-wide significant level. Next, we demonstrated that the model including rs6074022 only sufficiently described the association. From our analysis, we can speculate that the association between rs1883832 and MS was induced by LD, whereas rs6074022 was a marker in stronger LD with the functional variant or was the functional variant itself. Our results indicated that the functional variants were located in the upstream region of the gene CD40 and were in higher LD with rs6074022 than LD with rs1883832.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • CD40 Antigens / genetics*
  • Female
  • Haplotypes / genetics
  • Humans
  • Logistic Models
  • Male
  • Multiple Sclerosis / genetics*
  • Polymorphism, Single Nucleotide*
  • Russia


  • CD40 Antigens

Grants and funding

The study was supported by The Ministry of Education and Science of Russian Federation, project number 2012-1.5-12-000-1002-010 (government contract number 8490) and the grant of Presidium SBRAS (number 91). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.