HLA class III haplotypes in multicase rheumatoid arthritis families

• Published in: Human immunology Vol. 25; no. 2; pp. 75 - 85
• Main Authors: Fielder, A.H.L., Ollier, W., Lord, D.K., Burley, M.W., Silman, A., Awad, J., Festenstein, H., Batchelor, J.R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.1989; Elsevier Science
• Subjects: Alleles; Arthritis, Rheumatoid - genetics; Biological and medical sciences; Complement System Proteins - genetics; Diseases of the osteoarticular system; Gene Frequency; Haplotypes; Histocompatibility Antigens Class I - analysis; Histocompatibility Antigens Class II - analysis; HLA Antigens - analysis; Humans; Inflammatory joint diseases; Medical sciences; Pedigree; RA rheumatoid arthritis; Human; Immunopathology; HLA-System; Typing; Family study; Major histocompatibility system; Diseases of the osteoarticular system; Complement; Inflammatory joint disease; Proteins; Allele; Chronic; Immunogenetics; Gene; Rheumatoid arthritis; Alloantibody; Haplotype
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/0198-8859(89)90072-4

The class III complement proteins (C2, BF, C4A, and C4B) were studied in 57 multicase rheumatoid arthritis (RA) families. When the gene frequencies for RA probans were compared to a normal control panel (162 haplotypes), a significantly higher frequency of the rare variant C4B ∗3 was observed ( p < 0.05). No significant differences were seen for the other C2, BF, C4A, or C4B alleles. The most common haplotype found in the probands was HLA-Cw5, B44, C2 ∗C, BF ∗S, C4A ∗3, C4B ∗3, DR4, occurring with a frequency of 0.088. Haplotypes containing HLA-DR4 and Bw62 were found to carry either C4A ∗3, C4B ∗3; C4A ∗3, C4B ∗1; or C4A ∗4,C4B ∗2. When only haplotypes containing DR4 were compared between probands and controls, the frequency of the C4B ∗3-bearing haplotype remained higher in the probands. It is concluded that Bw62, C4A ∗3, C4B ∗3DR4 is a haplotype which is especially associated with RA. The low frequency in the RA population of this haplotype indicates that C4B ∗3 has a minor role in overall RA susceptibility.