COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese.
METHODS
Genetic screening of collagen 6A1 gene (COL6A1) in patients with diffuse idiopathic skeletal hyperostosis (DISH) recruited in Japan and the Czech Republic.


OBJECTIVE
To investigate allelic associations between DISH and nucleotide variants of COL6A1.


BACKGROUND
DISH is a skeletal hyperostotic disease characterized by ligamentous ossification of the anterolateral side of the spine. Ossification of the posterior longitudinal ligament (OPLL) is a related disorder with DISH, and COL6A1 was identified as a susceptibility gene to OPLL. COL6A1 was examined for susceptibility in DISH patients from Japan and the Czech Republic.


METHODS
Seven single nucleotide polymorphisms of COL6A1 were genotyped by direct sequencing. The allele frequencies were compared between 97 Japanese DISH patients and 298 Japanese controls, and between 96 Czech DISH patients and 96 Czech controls by chi2 test.


RESULTS
The intron 32 (-29) single nucleotide polymorphisms of COL6A1 was significantly associated with the Japanese DISH patients (chi2 = 9.33; P = 0.0022), but not with the Czech DISH patients.


CONCLUSIONS
Because COL6A1 could be a susceptibility to the occurrence of DISH and OPLL in the Japanese population, we consider that COL6A1 could be responsible for the hyperostotic state, leading to ectopic bone formation in the spinal ligament.
Tsukahara
So
S
Division of Genetic Diagnosis, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Miyazawa
Nobuhiko
N
Akagawa
Hiroyuki
H
Forejtova
Sarka
S
Pavelka
Karel
K
Tanaka
Toshihiro
T
Toh
Satoshi
S
Tajima
Atsushi
A
Akiyama
Iwao
I
Inoue
Ituro
I
D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D024142:Collagen Type VI / Q000235:genetics*; D018153:Czech Republic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D004057:Hyperostosis, Diffuse Idiopathic Skeletal / Q000235:genetics*; D007438:Introns; D008297:Male; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
C504344:COL6A2 protein, human; D024142:Collagen Type VI