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Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women

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Abstract

Spinal osteoarthritis including disc degeneration is a very common condition in the axial skeletons of aged people. Recently, spinal osteoarthritis has been shown to be influenced by specific genetic risk factors. Vertebral osteophytes, endplate sclerosis, and intervertebral disc narrowing are recognized as radiographic features of spinal disc degeneration. HAPLN1 is a key component of the cartilage extracellular matrix; thus, variations in this gene may affect the pathogenesis of cartilage-related diseases such as spinal degeneration. Here, we examine the association between an HAPLN1 gene polymorphism and the radiographic features of spinal degeneration. We evaluated the degree of endplate sclerosis, osteophyte formation, and disc space narrowing in 622 Japanese postmenopausal women. Four SNPs in the HAPLN1 gene—in the 5′ flanking region, intron 1, intron 2, and intron 4—were analyzed using the TaqMan polymerase chain reaction method. We found that compared to subjects with the CC or CT genotype, those with the TT genotype for an SNP at intron 2 (rs179851) were significantly overrepresented among the subjects with higher scores for osteophyte formation (P = 0.0001; odds ratio 2.12; 95% confidence interval 1.45–3.11, as determined by logistic regression analysis) and disc space narrowing (P = 0.0057; odds ratio 1.83; 95% confidence interval 1.19–2.83). Consistent with the involvement of the HAPLN1 gene in cartilage metabolism, a variation in a specific HAPLN1 gene locus may be associated with spinal degeneration.

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Acknowledgments

This work was partly supported by grants from the Japanese Ministry of Health, Labor, Welfare and the Ministry of Culture, Education, Sports, Science and Technology of Japan. This work was also partly supported by a grant from the Japan Anti-Aging Foundation.

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Authors and Affiliations

  1. Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bumkyo-ku, Tokyo, Japan

    Tomohiko Urano, Yasuyoshi Ouchi & Satoshi Inoue

  2. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Tomohiko Urano, Noriko Sasaki & Satoshi Inoue

  3. Department of Orthopedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Ken’ichiro Narusawa & Toshitaka Nakamura

  4. Research Institute and Practice for Involutional Diseases, Nagano, Japan

    Masataka Shiraki

  5. Department of Advanced Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan

    Takayuki Hosoi

  6. Research Center for Genomic Medicine, Saitama Medical School, Saitama, Japan

    Satoshi Inoue

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  1. Tomohiko Urano
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  2. Ken’ichiro Narusawa
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  3. Masataka Shiraki
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  4. Noriko Sasaki
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  5. Takayuki Hosoi
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  7. Toshitaka Nakamura
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  8. Satoshi Inoue
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Correspondence to Satoshi Inoue.

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Urano, T., Narusawa, K., Shiraki, M. et al. Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women. Eur Spine J 20, 572–577 (2011). https://doi.org/10.1007/s00586-010-1598-0

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  • DOI: https://doi.org/10.1007/s00586-010-1598-0

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