© 1995 British Society for Rheumatology
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RELATIVE CONTRIBUTIONS OF HLA-DQA AND COMPLEMENT C4A LOCI IN DETERMINING SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS
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*University of Manchester Rheumatic Diseases Centre, Hope Hospital Eccles Old Road, Salford M6 8HD
ARC Epidemiology Research Unit, Stopford Building, University of Manchester Oxford Road, Manchester M13 9PT
Department of Rheumatology, Royal North Shore Hospital St Leonards, NSW 2065, Australia
Department of Rheumatology, Pinderfields NHS Trust Aberford Road, Wakefield, W. Yorks
Correspondence to:
Correspondence to: E. J. Davies, ARC Epidemiology Research Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT.
The objective of this study was to reassess the role of C4A null alleles in systemic lupus erythematosus (SLE) susceptibility after taking into account the association of DQA*0501 with this disease. The frequency of C4A null alleles in 82 SLE patients and 59 controls was determined using both immunofixation and a Taql RFLP method. HLA-DQA and DQB alleles were identified by sequence-specific oligonuclcotide typing. Empirical logistic analysis was used to assess the interactive effects of C4 and DQA alleles. It was found that the strongest association with SLE was for the combination of DQA*0501 and C4A*Q0 [odds ratio (OR) = 5.4, 95% confidence interval (CI) 2.5–11.7]. Both DQA*0501 (P = 0.02) and C4A*Q0 (P = 0.03) appeared to have significant individual effects on SLE susceptibility, with a significant statistical interaction between the two loci (P = 0.01). However, when anti-La antibody negative patients were examined only C4A*Q0 had a significant individual effect (P = 0.04). A significant statistical interaction between DQA*0501 and C4A*Q0 was again detected (P = 0.02). These results support the hypothesis that susceptibility to SLE is influenced by several genes with differing functions: HLA-DQA*0501 may predispose to autoantibody formation while C4A*Q0 impairs immune complex clearance.
KEY WORDS: Systemic lupus erythematosus, Major histocompatibility complex, Complement
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