HLA-DRB1 alleles encoding an aspartic acid at position 70 protect against development of rheumatoid arthritis

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Abstract

OBJECTIVE: To determine whether the association between rheumatoid arthritis (RA) and HLA-DRB1 is influenced by the amino acid residue encoded at position 70 (beta70) of the third hypervariable region (HVR3) of the HLA-DRbeta chain. METHODS: The frequencies of HLA-DRB1 alleles encoding different amino acid residues at beta70 were compared between patients with RA and controls in a population from the UK and in a confirmatory population from northwestern Spain. HLA-DRB1 typing was done by polymerase chain reaction methods on 476 clinic based patients with RA and 180 healthy controls from Staffordshire and Cheshire in the UK, and on 179 clinic patients and 145 controls from Lugo, Spain. Associations were investigated using chi-square analyses and regression analyses. The extended Mantel-Haenszel procedure was used for trend analysis. RESULTS: Carriage of 2 shared epitope (SE)+ alleles encoding a glutamine at beta70 (Q70SE+/Q70SE+) was associated with the greatest risk of RA in the UK and Spanish population (odds ratios 7.93 and 4.66, respectively), while possession of 2 SE- alleles encoding an aspartic acid at beta70 (D70SE-D70SE-) was associated with the lowest risk (OR 0.23 and 0.34, respectively). In individuals carrying one SE+ allele and an accompanying D

Keyword(s)

Alleles; Amino Acid Sequence; Arthritis; Arthritis,Rheumatoid; Aspartic Acid; England; Epitope Mapping; Epitopes; Female; Genetic Predisposition to Disease; Genotype; Great Britain; HLA-DR Antigens; Human; Male; Odds Ratio; Polymerase Chain Reaction; Rheumatology; Risk; Spain; Support,Non-U.S.Gov't; analysis; genetics; methods

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