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 hierarchial 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 less than 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.
Neuroimmunology Laboratory, La Trobe University, Bundoora, Victoria, Australia.
M A
MA
Sherritt
J
J
Oksenberg
N K
NK
de Rosbo
C C
CC
Bernard
D015415:Biomarkers; D015139:Blotting, Southern; D016022:Case-Control Studies; D015342:DNA Probes; D004198:Disease Susceptibility; D006682:HLA-DP Antigens / Q000276:immunology*; D059868:HLA-DP beta-Chains; D015802:HLA-DR2 Antigen / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D009103:Multiple Sclerosis / Q000276:immunology*; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D015415:Biomarkers; D015342:DNA Probes; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; D015802:HLA-DR2 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta