COMPOUND HETEROZYGOSITY FOR THE SHARED EPITOPE AND THE RISK AND SEVERITY OF RHEUMATOID-ARTHRITIS IN EXTENDED PEDIGREES

Citation
Je. Mcdonagh et al., COMPOUND HETEROZYGOSITY FOR THE SHARED EPITOPE AND THE RISK AND SEVERITY OF RHEUMATOID-ARTHRITIS IN EXTENDED PEDIGREES, British journal of rheumatology, 36(3), 1997, pp. 322-327
Citations number
26
Categorie Soggetti
Rheumatology
ISSN journal
02637103
Volume
36
Issue
3
Year of publication
1997
Pages
322 - 327
Database
ISI
SICI code
0263-7103(1997)36:3<322:CHFTSE>2.0.ZU;2-U
Abstract
The objective was to explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis (RA). The population compris ed 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-DRB104 variants was perfo rmed using the Multiplex ARMS-RFLP technique. Compound heterozygote in dividuals 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 suggest ed. Individuals carrying no SE alleles expressed milder disease, as me asured by the Spread Severity (SS) index, compared to compound heteroz ygotes (P = 0.045). Compound heterozygosity was not invariably associa ted 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. Inher iting two different SE-bearing alleles results in an increased risk of RA and, on average, greater disease severity. This is not, however, i nvariably associated with severe disease, making it of limited use as a predictor of prognosis.