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Q89R Polymorphism in the LDL Receptor-Related Protein 5 Gene Is Associated With Spinal Osteoarthritis in Postmenopausal Japanese Women

Urano, Tomohiko, MD, PhD*; Shiraki, Masataka, MD, PhD; Narusawa, Ken'ichiro, MD, PhD; Usui, Takahiko, MD*; Sasaki, Noriko, BS*; Hosoi, Takayuki, MD, PhD§; Ouchi, Yasuyoshi, MD, PhD*; Nakamura, Toshitaka, MD, PhD; Inoue, Satoshi, MD, PhD*∥

doi: 10.1097/01.brs.0000251003.62212.5b
Basic Science

Study Design. An association study investigating the genetic etiology for spinal osteoarthritis.

Objective. To determine the association of single-nucleotide polymorphism (SNP) causing an amino-acid change (Q89R) in the low-density lipoprotein receptor-related protein 5 (LRP5) coding region with spinal osteoarthritis.

Summary of Background Data. Wnt/β-catenin signaling pathway regulates bone density through a Wnt coreceptor LRP5. This pathway is also involved in cartilage development and homeostasis, suggesting that genetic variation in LRP5 gene may affect the pathogenesis of cartilage-related diseases, such as osteoarthritis.

Methods. We evaluated the presence of osteophytes, endplate sclerosis, and narrowing of disc spaces in 357 Japanese postmenopausal women. Missense coding SNP for Q89R of LRP5 gene was determined using TaqMan polymerase chain reaction (PCR) method.

Results. We found that subjects without the R allele (QQ; n = 321) had a significantly lower osteophyte formation score than did subjects bearing at least one R allele (QR + RR; n = 36) (7.80 vs. 10.89, P = 0.0019 by analysis of covariance).

Conclusions. We suggest that a genetic variation at the LRP5 gene locus is associated with spinal osteoarthritis, in line with the involvement of the LRP5 gene in the bone and cartilage metabolism.

Wnt/β-catenin signaling pathway regulates bone and cartilage metabolism. The single nucleotide polymorphism causing an amino-acid change (Q89R) in LRP5 gene, a Wnt coreceptor, was associated with spinal osteophytosis in Japanese postmenopausal women. We suggest that a genetic variation at the LRP5 gene locus is associated with spinal osteoarthritis.

From the *Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; †Research Institute and Practice for Involutional Diseases, Nagano, Japan; ‡Department of Orthopedic Surgery, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan; §Department of Advanced Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan; and ∥Research Center for Genomic Medicine, Saitama Medical School, Saitama, Japan.

Acknowledgment date: October 28, 2005. First revision date: February 23, 2006. Acceptance date: March 2, 2006.

Supported in part by grants from the Japanese Ministry of Health, Labor, Welfare and Japan Society for the Promotion of Science and by a grant of the Genome Network Project from the Ministry of Culture, Education, Sports, Science and Technology of Japan.

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Satoshi Inoue, MD, PhD, Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bumkyo-ku, Tokyo, Japan; E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.