Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis.
Osteoprotegerin (OPG), a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily, is considered to play an important role in the regulation of bone resorption by modifying osteoclast differentiation. Overexpression of OPG in mice has been reported to result in osteopetrosis, whereas targeted disruption of OPG in mice has been associated with osteoporosis. Accordingly, OPG could be a strong candidate gene for susceptibility to human osteoporosis. Here, we analyzed whether OPG is involved in the etiology of osteoporosis using both linkage and association analyses. We recruited 164 sib pairs in Gunma prefecture, which is located in the central part of Honshu (mainland Japan), for a linkage study, and 394 postmenopausal women in Akita prefecture, which is in the northern part of Honshu, for an association study. We identified two microsatellite polymorphisms in the linkage study, and six single-nucleotide polymorphisms (SNPs) in the OPG region for the association study. Although, no evidence of significant linkage between OPG and osteoporosis was found, a possible association of one SNP, located in the promoter region of the gene, was identified. A haplotype analysis with the six SNPs revealed that four major haplotypes account for 71% of the alleles in the Japanese population.
Department of Public Health, Asahikawa Medical College, 2-1-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan.
Hioryuki
H
Ohmori
Yoshio
Y
Makita
Makiko
M
Funamizu
Kenzou
K
Hirooka
Takayuki
T
Hosoi
Hajime
H
Orimo
Takao
T
Suzuki
Katsunori
K
Ikari
Toshiaki
T
Nakajima
Ituro
I
Inoue
Akira
A
Hata
D001483:Base Sequence; D015519:Bone Density / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D015663:Osteoporosis, Postmenopausal / Q000235:genetics*; D053244:Osteoprotegerin; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human