Genetic mapping of ossification of the posterior longitudinal ligament of the spine.
Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provided by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P = .000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P = .0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p.
Koga
H
H
Department of Orthopedic Surgery, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
Sakou
T
T
Taketomi
E
E
Hayashi
K
K
Numasawa
T
T
Harata
S
S
Yone
K
K
Matsunaga
S
S
Otterud
B
B
Inoue
I
I
Leppert
M
M
D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003094:Collagen / Q000235:genetics; D008040:Genetic Linkage; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D017887:Ossification of Posterior Longitudinal Ligament / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D011859:Radiography
D006680:HLA Antigens; D003094:Collagen