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Compound heterozygosity for the shared epitope and the risk and severity of rheumatoid arthritis in extended pedigrees

Compound heterozygosity for the shared epitope and the risk and severity of rheumatoid arthritis in extended pedigrees

British Journal of Rheumatology 36(3): 322-327

The objective was to explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis (RA). The population comprised extended pedigrees of 17 multicase RA families. Family members were genotyped for both HLA-DRB1 alleles using restriction fragment length polymorphism (RFLP). Identification of HLA-DRB1*04 variants was performed using the Multiplex ARMS-RFLP technique. Compound heterozygote individuals carrying two different alleles containing the shared epitope (SE) were at greatest risk of developing RA (odds ratio = 36, 95% CI 9.1-143). A synergistic or additive effect of these alleles is suggested. Individuals carrying no SE alleles expressed milder disease, as measured by the Spread Severity (SS) index, compared to compound heterozygotes (P = 0.045). Compound heterozygosity was not invariably associated with severe disease with six (50%) having clinically mild disease at a median age of 57.5 yr and median disease duration of 16 yr. Inheriting two different SE-bearing alleles results in an increased risk of RA and, on average, greater disease severity. This is not, however, invariably associated with severe disease, making it of limited use as a predictor of prognosis.

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Accession: 008369366

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PMID: 9133963

DOI: 10.1093/rheumatology/36.3.322

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