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

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.

• Authors: R Said-Nahal, C Miceli-Richard, C Gautreau, R Tamouza, N Borot, R Porcher, D Charron, M Dougados, M Breban
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 61 Issue 3 Pg. 201-6 (Mar 2002) ISSN: 0003-4967 [Print] England
• PMID: 11830423 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA Antigens
• HLA-A Antigens
• HLA-B27 Antigen
• HLA-C Antigens
• HLA-DR4 Antigen

Topics

• Adult
• Alleles
• Binomial Distribution
• Chi-Square Distribution
• Confidence Intervals
• Female
• France
• HLA Antigens (genetics)
• HLA-A Antigens (genetics)
• HLA-B27 Antigen (genetics)
• HLA-C Antigens (genetics)
• HLA-DR4 Antigen (genetics)
• Haplotypes
• Humans
• Linkage Disequilibrium
• Male
• Middle Aged
• Odds Ratio
• Pedigree
• Spondylarthropathies (genetics)