Association of common T cell activation gene polymorphisms with multiple sclerosis in Australian patients

J Neuroimmunol. 2004 Mar;148(1-2):218-30. doi: 10.1016/j.jneuroim.2003.12.003.


Susceptibility to multiple sclerosis (MS) may be influenced by the interaction of several genes within a biological pathway. T cell activation and costimulation may be potentially important in MS pathogenesis. We have therefore investigated associations between MS and polymorphisms in the CD152 (CTLA-4), CD28, CD80 and CD86 genes in Australian patients. We found no significant MS association with CTLA-4 exon 1 +49 alleles, and meta-analysis showed no significant association across nine comparable datasets (OR=1.04, p=0.54), nor with primary progressive MS across seven datasets (OR=1.19, p=0.21). Haplotype analysis showed a trend towards a decrease of the CTLA-4-1722C, -1577G, +49G haplotype in +49 G positive MS patients compared with controls (p=0.06). Screening of CD28, CD80 and CD86 genes identified novel polymorphisms in the putative promoter regions of CD28 (-372 G/A) and CD86 (exon 2 -359 deletionAAG). There was a significant increase of the CD28 -372 G allele frequency in MS patients vs. controls (p=0.045) and a trend towards a significant interaction between this allele and the CTLA-4 +49 G allele (OR=4.00, p=0.058). Our results suggest that the CTLA-4 +49 alone is not associated with overall susceptibility to MS, but may be important in clinical subsets of patients and/or may interact epistatically with other gene polymorphisms.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / metabolism
  • Australia / epidemiology
  • B7-1 Antigen / genetics
  • B7-2 Antigen
  • CD28 Antigens / genetics*
  • CTLA-4 Antigen
  • Databases as Topic / statistics & numerical data
  • Exons / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Haplotypes
  • Humans
  • Membrane Glycoproteins / genetics
  • Meta-Analysis as Topic
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Polymorphism, Genetic*
  • T-Lymphocytes / metabolism


  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Membrane Glycoproteins