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The Association of Lumbar Disc Disease with Vitamin-D Receptor Gene Polymorphism

Investigation performed at the Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan

Yoshiharu Kawaguchi, MD, PhD
Masahiko Kanamori, MD, PhD
Hirokazu Ishihara, MD, PhD
Kazuo Ohmori, MD, PhD
Tomoatsu Kimura, MD, PhD
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine, 2630, Sugitani, Toyama 930-0194, Japan. E-mail address for Y. Kawaguchi: zenji{at}ms.toyama-mpu.ac.jp

Hisao Matsui, MD, PhD
Orthopaedic Surgery, Takaoka City Hospital, 4-1, Takaramachi, Takaoka, Toyama 933-0064, Japan

In support of their research or preparation of this manuscript, one or more of the authors received a grant-in-aid for scientific research (11770794) from the Japanese Ministry of Education, Science and Culture in 1999-2000. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Although the etiology of lumbar disc disease is unknown, it has been suggested that a genetic factor contributes to its development. Recently, some genetic polymorphisms have been found to be related to clinical disorders. We investigated the association between vitamin-D receptor gene and estrogen receptor gene polymorphisms and lumbar disc disease in young adults.

Methods: The participants included 205 young adults (166 women and thirty-nine men) with or without low-back problems. A magnetic resonance imaging scan of the lumbar spine was performed for all subjects, and the grade of disc degeneration was determined, according to the four-grade classification system of Schneiderman et al. The presence or absence of disc herniation was also evaluated. Genomic DNA was extracted from peripheral blood samples. The polymorphisms of the vitamin-D receptor and estrogen receptor genes were detected with use of a polymerase-chain-reaction assay. The restriction fragment length polymorphisms (RFLPs) for the vitamin-D receptor gene were analyzed by TaqI and ApaI restriction enzymes. XbaI and PvuII restriction enzymes were used for the estrogen receptor gene analysis. The distribution of polymorphism in subjects with disc degeneration and/or disc herniation was compared with that in the normal subjects.

Results: The allelic frequencies of both vitamin-D receptor gene and estrogen receptor gene polymorphisms were similar to those in previous analyses of Japanese subjects. The allelic variation in the vitamin-D receptor gene was associated with multilevel and severe disc degeneration and disc herniation. The Tt allele was found to be more frequently associated with multilevel disc disease, severe disc degeneration, and disc herniation than was the TT allele. No additional associations were found.

Conclusions: This study revealed that the Tt allele of the vitamin-D receptor gene was more frequently associated with multilevel and severe disc degeneration and disc herniation than was the TT allele, pointing to an increased risk of disc disease at an early age in subjects with the Tt allele in the vitamin-D receptor gene.

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