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More MS news articles for February 2004

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

J Neuroimmunol. 2004 Mar;148(1-2):218-30
Teutsch SM, Booth DR, Bennetts BH, Heard RN, Stewart GJ.
Institute for Immunology and Allergy Research (Westmead Millennium Institute), Level 2 ICPMR, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.

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.