INFLUENCE OF HLA-DR2, HLA-DPW4, AND T-CELL RECEPTOR ALPHA-CHAIN GENES ON THE SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS

In view of our recent report that T cell receptor (TCR) alpha-chain restriction fragment length polymorphism (RFLP) is associated with multiple sclerosis (MS), we have assessed the possibility that HLA-DR2, HLA-DPw4, and TCR alpha-chain RFLPs may interact to increase the risk of developing MS. Detection of TCR alpha-chain polymorphisms, and HLA-DR and -DP typing were carried out by RFLP analysis on MS patients and healthy controls from the Melbourne metropolitan area. Interaction effects among these loci in producing susceptibility to MS were assessed by hierarchical log-linear analysis. Although HLA-DR2 was significantly associated with MS (chi-2 = 9.30, P = 0.002), no interactive effect between MS and HLA-DPw4 was observed. Significant interactions were observed with MS and both C-alpha and V-alpha, with the strongest effect seen with C-alpha (chi-2 = 21.30, P < 0.001). The combination of DR2/C-alpha imparted a relative risk of 47. However, when the data were analysed for four and three way interactions, no significant effects were seen with MS, DR2, DPw4, V-alpha, and C-alpha, implying that the combined presence of these polymorphic markers is not essential for increasing susceptibility to MS.