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A Replication Study for Association of 53 Single Nucleotide Polymorphisms in a Scoliosis Prognostic Test With Progression of Adolescent Idiopathic Scoliosis in Japanese

Ogura, Yoji MD*,†; Takahashi, Yohei MD, PhD*,†; Kou, Ikuyo PhD*; Nakajima, Masahiro PhD*; Kono, Katsuki MD; Kawakami, Noriaki MD, DMSc§; Uno, Koki MD; Ito, Manabu MD, PhD; Minami, Shohei MD, PhD**; Yanagida, Haruhisa MD††; Taneichi, Hiroshi MD‡‡; Yonezawa, Ikuho MD§§; Tsuji, Taichi MD§; Suzuki, Teppei MD; Sudo, Hideki MD, PhD; Kotani, Toshiaki MD, PhD**; Watanabe, Kota MD, PhD; Chiba, Kazuhiro MD, PhD¶¶; Toyama, Yoshiaki MD, PhD; Matsumoto, Morio MD, PhD; Ikegawa, Shiro MD, PhD*

doi: 10.1097/BRS.0b013e3182947d21

Study Design. A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS).

Objective. To determine whether the association of 53 SNPs with curve progression reported in white patients with AIS are replicated in Japanese patients with AIS.

Summary of Background Data. Predicting curve progression is important in clinical practice of AIS. The progression of AIS is reported to be associated with a number of genes. Associations with 53 SNPs have been reported, and the SNPs are used for a progression test in white patients with AIS; however, there has been no replication study for their association.

Methods. We recruited 2117 patients with AIS with 10° or more (Cobb angle) of scoliosis curves. They were divided into progression and nonprogression groups according to their Cobb angle. We defined the progression of the curve as Cobb angle more than 50° for skeletally mature subjects and more than 40° for immature patients, subjects. We defined the nonprogression of the curve as Cobb angle 50° or less only for skeletally mature subjects. Of the 2117 patients, 1714 patients with AIS were allocated to either the progression or nonprogression group. We evaluated the association of 53 SNPs with curve progression by comparing risk allele frequencies between the 2 groups.

Results. We evaluated the progression (N = 600) and nonprogression (N = 1114) subjects. Their risk allele frequencies were not different significantly. We found no replication of the association on AIS curve progression in any of the SNPs.

Conclusion. The associations of the 53 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression.

Level of Evidence: N/A

Supplemental Digital Content is Available in the Text.Adolescent idiopathic scoliosis (AIS) has a strong genetic predisposition, and a number of single nucleotide polymorphisms (SNPs) were reported to have association with curve progression. We investigated the associations of 53 SNPs with AIS curve progression previously reported in Caucasian patients with AIS; however, they were not replicated in Japanese patients with AIS.

*Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan

Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan

Department of Orthopaedic Surgery, Eiju General Hospital, Tokyo, Japan

§Department of Orthopaedic Surgery, Meijo Hospital, Nagoya, Japan

Department of Orthopaedic Surgery, National Hospital Organization, Kobe Medical Center, Kobe, Japan

Department of Advanced Medicine for Spine and Spinal Cord Disorders, Hokkaido University Graduate School of Medicine, Sapporo, Japan

**Department of Orthopaedic Surgery, Seirei Sakura Citizen Hospital, Sakura, Japan

††Department of Orthopaedic Surgery, Fukuoka Children's Hospital, Fukuoka, Japan

‡‡Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, Mibu, Japan

§§Department of Orthopaedic Surgery, Juntendo University School of Medicine, Tokyo, Japan; and

¶¶Department of Orthopaedic Surgery, Kitasato Institute Hospital, Tokyo, Japan.

Address correspondence and reprint requests to Shiro Ikegawa, MD, PhD, Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, 4-6-1 Sirokanedai, Minato-ku, Tokyo 108-8639, Japan; E-mail:

Acknowledgment date: January 8, 2013. First revision date: March 1, 2013. Second revision date: March 20, 2013. Acceptance date: March 28, 2013.

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

Grant-in-Aid for Scientific Research B (24390357) and Keio Gijuku Academic Development Funds were received to support this work.

Relevant financial activities outside the submitted work: consultancy.

© 2013 by Lippincott Williams & Wilkins