HLA in ankylosing spondylitis: is HLA-B27 the only MHC gene involved in disease pathogenesis?
Linkage analysis of HLA haplotypes, HLA-B27 subtypes, and a 9.2-kb PvuII B7 restriction fragment length polymorphism (RFLP) (shown previously to be associated with peripheral arthritis in ankylosing spondylitis [AS]) in 115 relatives from 12 multiplex spondyloarthropathy (SNSA) and 2 B27-positive control families showed AS to be linked to HLA-B27 haplotypes. The RFLP segregated with HLA-A3- and HLA-A9-bearing haplotypes (lod score, 10.98; odds in favor of linkage, 9.2 x 10(10):1), although its linkage to AS or other SNSA per se was not seen. The association of HLA-A3/A9 with the RFLP was also seen in 52 AS patients and 92 controls, although no HLA-A, -B, -C, or -DR allele (other than HLA-B27) was significantly increased in frequency. The HLA-B27 subtype seen on all but one of the haplotypes studied was B*2705, the sole exception being HLA-B*2702. Although not ruling out a second HLA-A-linked gene influencing the clinical expression of AS, these data fail to support the role of a second MHC-associated gene in the pathogenesis of AS per se.
Reveille
J D
JD
Department of Medicine, University of Texas Health Science Center at Houston 77225.
Suarez Almazor
M E
ME
Russell
A S
AS
Go
R C
RC
Appleyard
J
J
Barger
B O
BO
Acton
R T
RT
Koopman
W J
WJ
McDaniel
D O
DO
D000483:Alleles; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005805:Genes, MHC Class I / Q000502:physiology*; D008040:Genetic Linkage; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015234:HLA-A Antigens / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015796:HLA-B27 Antigen / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D013167:Spondylitis, Ankylosing / Q000209:etiology* / Q000235:genetics / Q000276:immunology
D006680:HLA Antigens; D015234:HLA-A Antigens; D015796:HLA-B27 Antigen; D004247:DNA