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Rheumatoid arthritis (RA) is a common disease of unknown aetiology which usually causes progressive destruction of the joints. Familial aggregation, twin studies and segregation analyses suggest that there is a genetic component to RA and the HLA-DRB1 locus in the major histocompatibility complex on chromosome 6 has been shown to be linked to, and associated with, RA susceptibility. It is likely that other genes with weaker effects are also involved, which may be difficult to detect using conventional parametric and non-parametric linkage methods. We have implemented the combined sib-TDT and TDT, in addition to parametric and non-parametric linkage methods, to investigate the candidate genes of the interleukin-1 (IL-1) gene cluster on chromosome region 2q13, since IL-1 is an important cytokine in the control of the inflammatory response that is central to RA pathology. Several tightly linked IL-1 cluster markers yielded suggestive evidence for linkage in the combined TDT in those families in which affected siblings did not share two HLA-DRB1 alleles identical by descent. The evidence was significant in those with severe disease, as assessed by the presence of bone erosions. In contrast, there was no evidence of linkage using non-parametric linkage analysis, but parametric analysis revealed weak evidence of linkage when marker-trait disequilibrium was incorporated into the analysis. The data provide preliminary evidence for linkage of genes of the IL-1 cluster to RA and suggest a possible role for this region in severe erosive disease.

Original publication

DOI

10.1093/hmg/8.9.1707

Type

Journal article

Journal

Human molecular genetics

Publication Date

09/1999

Volume

8

Pages

1707 - 1713

Addresses

Division of Molecular and Genetic Medicine, Royal Hallamshire Hospital, University of Sheffield, Sheffield S10 2JF, UK. a.cox@sheffield.ac.uk

Keywords

Chromosomes, Human, Pair 2, Humans, Arthritis, Rheumatoid, Genetic Markers, Interleukin-1, HLA-DR Antigens, Genotype, Haplotypes, Lod Score, Polymorphism, Genetic, Multigene Family, Genetic Linkage