T cell receptor beta chain genotyping in Australian relapsing-remitting multiple sclerosis patients

This study focused on susceptibility to MS within the beta-chain of the T-c ell antigen receptor (TCRB locus, 7q35) in a cohort of 122 RR-MS patients c ompared with 96 normal individuals using biallelic polymorphisms across the bv8s1(V beta 8.1) to bv11s1 (V beta 11) TCRB subregion. The markers bv6s5, bv8s1, bv10s1, bv15s1 and bv3s1 were studied for allele and genotype frequ encies; haplotypes were assigned with combinations of two of these markers and stratification for HLA-DR15 was also performed. Linkage disequilibrium was found between alleles of the bv8s1, bv10s1/bv15s1 and bv3s1 loci in bot h patients and controls. An increase among RR-MS patients in the allele fre quency of bv8s1*2 (P=0.03) and the haplotype bv8s1*2/bv3s/*/ (P=0.006) was noted and both were found to be statistically significant In the DR15-posit ive group, the association between TCRB and MS was seen with the bv8s1*2 al lele (P-uc=0.05) and the bv8s1*2/bv10s1 hoplotypes (P-uc=0.048), while the hoplotype associations seen among DR15-negative RR-MS patients included the bv3s/*/ allele (bv10s/*/ bv3s/*// P-uc=0.022; bv8s/*2/bv3s/*/, P-uc=0.048) . These results support the involvement of the TCRB region in MS susceptibi lity and encourage further study of the variable gene segments in this regi on.