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. 2002 Mar;61(3):201–206. doi: 10.1136/ard.61.3.201

The role of HLA genes in familial spondyloarthropathy: a comprehensive study of 70 multiplex families

R Said-Nahal 1, C Miceli-Richard 1, C Gautreau 1, R Tamouza 1, N Borot 1, R Porcher 1, D Charron 1, M Dougados 1, M Breban 1
PMCID: PMC1754018  PMID: 11830423

Abstract

Objectives: To investigate whether HLA alleles, other than HLA-B27, influence predisposition to spondyloarthropathy (SpA) in multiplex families.

Methods: Seventy French families with at least two affected SpA members were recruited. Patients, and their first degree relatives were typed for HLA-A, B, C, and DR, and extended HLA haplotypes were determined. The distribution of HLA-A, C, and DR alleles carried on HLA-B27+ haplotypes in SpA families was compared with the distribution of these alleles among HLA-B27+ haplotypes in the French general population. Contribution to SpA susceptibility of HLA-A, B, C, and DR alleles, other than HLA-B27, was tested by transmission disequilibrium test. The contribution of HLA alleles to specific presentation features of SpA was examined.

Results: Frequencies of HLA-A, C, and DR alleles carried on HLA-B27+ haplotypes from SpA families were comparable with those seen in the French population, except for DR13 which was overrepresented among patients (pcorr<0.001). Most interestingly, the HLA-DR4 allele was transmitted in excess to patients with SpA, independently of linkage to HLA-B27 (pcorr=0.05), and in a direction opposite to that for HLA-B27+ unaffected siblings (pcorr=0.01). Finally, the distribution of HLA alleles was not related to the presentation feature of SpA.

Conclusion: HLA predisposition to familial SpA appears not to be limited to HLA-B27, but some HLA-DR alleles also have a significant influence. In particular, HLA-DR4 contributes significantly to a genetic predisposition to SpA, which may have implications in our understanding of SpA pathogenesis.

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Selected References

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