Additional genetic susceptibility for rheumatoid arthritis telomeric of the DRB1 locus

Open Access
Publisher Website
Google Scholar
Abstract
Objective Rheumatoid arthritis (RA) has an estimated genetic contribution of 30–50%, approximately one‐third of which arises from the major histocompatibility complex on 6p21.3. Many studies have implicated alleles of DRB1 that encode a shared epitope. However, several recent studies have suggested that additional telomeric genetic influences may exist. In this study, we sought to investigate whether a separate non‐DRB1 effect could be detected and to determine its likely location. Methods We typed 13 single‐nucleotide polymorphisms, located mainly in the telomeric class III region of the major histocompatibility complex, in 164 British Caucasian families with RA that had at least 1 affected offspring and used unconditioned and DRB1‐conditioned transmission disequilibrium tests (TDTs). Results Unconditioned TDTs revealed overtransmission of shared epitope alleles (P = 2.12 × 10−5) and an allele of the HLA–B–associated transcript 1 (BAT1) gene in the telomeric class III region (P = 0.009). Using a DRB1‐conditioned TDT to assess whether an independent effect existed, we detected unequal transmission of alleles of lymphocyte‐specific transcript 1 (P = 0.004), BAT1 (P = 0.003), and PG8 (P = 0.003). Conclusion At least 1 additional non‐DRB1 susceptibility locus for RA exists in an interval that encompasses the junction of the class III and I regions. This is a genomic segment of high linkage disequilibrium containing a large number of poorly characterized immunomodulatory genes.

This publication has 34 references indexed in Scilit: