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A study of C4AQ0 and MHC haplotypes in Icelandic multicase families with systemic lupus erythematosus

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Authors
Kristjansdottir, H
Bjarnadottir, K
Hjalmarsdottir, I B
Grondal, G
Arnason, A
Steinsson, K
Issue Date
2000-11-01

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A study of C4AQ0 and MHC haplotypes in Icelandic multicase families with systemic lupus erythematosus. 2000, 27 (11):2590-6 J. Rheumatol.
Abstract
OBJECTIVE: To study MHC haplotypes and C4AQ0 in Caucasian multicase systemic lupus erythematosus (SLE) families from Iceland. METHODS: Eight families with 26 SLE patients, 98 non-SLE first-degree relatives, and a control group were studied. For statistical analysis one SLE patient and one first-degree relative were randomly chosen from each family. C4 allotyping was performed by protein electrophoresis, HLA typing of class I by the lymphocytotoxicity test, and typing of class II alleles with polymerase chain reaction with sequence specific primers. RESULTS: Six of the 8 families showed a high background of C4A protein deficiency (C4AQ0) and a significant increase was seen in C4AQ0 in the randomly chosen group of patients. A similar tendency that was statistically nonsignificant was seen in first-degree relatives. In the SLE patients C4AQ0 was found on several MHC haplotypes. Half the patients with C4A protein deficiency carry C4AQ0 on the classical C4A deletion haplotype B8-C4AQ0-C4B1-DR3 or variants of it, and the remaining C4A deficient patients on other non-DR3 carrying haplotypes. The transmission of C4AQ0 from parents to patients was in most cases through the family line, although in some instances it originates from outside the multicase SLE family through spouses married into the family. CONCLUSION: In these Caucasian multicase SLE families from Iceland, C4AQ0 shows weaker linkage disequilibrium with DR3 than reported in studies on other white populations, emphasizing the role of ethnicity. The common factor in the MHC haplotypes studied is C4AQ0, supporting a hypothesis that C4AQ0 may be an independent risk factor for SLE.
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