Association of HTRA1 promoter polymorphism with spinal disc degeneration in Japanese women.
HTRA1 (high-temperature requirement A1) has been implicated in the modulation of various disease pathologies. HTRA1 expression is upregulated in osteoarthritic joints, suggesting that it may contribute to the development of this debilitating disease. Moreover, recent reports have shown that the rs11200638, a single nucleotide polymorphism (SNP) in the promoter region of the HTRA1 gene, is strongly associated with an increased prevalence of age-related macular degeneration (AMD). In the present study, we examined the expression of the HTRA1 in human primary chondrocytes and an association between the rs11200638 SNP and radiographic features of spinal disc degeneration in 513 postmenopausal Japanese women. HTRA1 mRNA was detected and increased by TGF-beta treatment in human primary chondrocytes. As an association study of rs11200638 SNP in the HTRA1 gene, the subjects without the G allele (AA; n = 89) had a significantly higher spinal disc space narrowing score than the subjects bearing at least one G allele (GG + GA; n = 424) (P = 0.0292). We found that subjects without the G allele (AA) were significantly overrepresented in the subjects having a higher (> or =4) disc space narrowing score (P = 0.013; odds ratio 1.97; 95% confidence interval 1.15-3.37 by logistic regression analysis). A genetic variation at the HTRA1 gene promoter locus is associated with spinal disc degeneration, suggesting an involvement of the HTRA1 gene in osteoarthritis.
Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Tomohiko
T
Urano
Ken'ichiro
K
Narusawa
Satomi
S
Kobayashi
Masataka
M
Shiraki
Kuniko
K
Horie-Inoue
Noriko
N
Sasaki
Takayuki
T
Hosoi
Yasuyoshi
Y
Ouchi
Toshitaka
T
Nakamura
Satoshi
S
Inoue
D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007403:Intervertebral Disc / Q000000981:diagnostic imaging; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000235:genetics*; D007564:Japan; D008875:Middle Aged; D009045:Motor Endplate / Q000000981:diagnostic imaging / Q000473:pathology; D055013:Osteoarthritis, Spine / Q000235:genetics; D054850:Osteophyte / Q000000981:diagnostic imaging / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D012598:Sclerosis / Q000000981:diagnostic imaging / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index
D012333:RNA, Messenger; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases