Association of the Tag SNPs in the Human Skt Gene with Lumbar Disk Herniation

Introduction Lumbar disk herniation (LDH) is a major cause of low back pain and unilateral leg pain. Although the etiology is unknown, it has been suggested that a genetic factor contributes to the development of LDH. Sickle tail (Skt) protein shows specific expression in mice nucleus pulposus (NP) cells. SktGt mice were established through a gene-trap mutagenesis in embryonic stem cells. Skt homozygous mutant mice showed late-onset intervertebral disk abnormalities. The purpose of this study was to evaluate whether the human Skt gene was involved in the etiology of LDH. A case-control association study was performed in Japanese and Finnish populations. Materials and Methods On the basis of information in the International HapMap Project database, we selected SNPs with minor allele frequencies of >10%. A total of 68 tag SNPs were selected. We recruited 525 cases and 564 controls for the first screen and 337 cases and 332 controls for the replication study. The diagnosis of LDH required the following: (1) positive MRI findings for LDH; (2) treatment and monitoring for >1 year by orthopedic surgeons; and (3) a history of unilateral leg pain for a period >3 months. The Finnish population consisted of 257 patients and 249 controls. Results Three SNPs were significantly associated with LDH. The SNP rs16924573 showed the most significant association with LDH ( p = 0.0015). The association was replicated in a Finnish case-control population ( p = 0.026). The combined p value of the two population by meta-analysis is 0.00040 (OR, 1.34; 95% CI, 1.14–1.58). Conclusion Our data indicate that Skt is involved in the etiology of LDH. Skt contains a proline-rich region and a coiled-coil domain. It is possible that impaired Skt may not be capable of forming cytoskeleton complexes or interacting with other proteins. Such malfunctions of Skt could lead to LDH through NP dysfunction. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Karasugi T, Semba K, Hirose Y, et al. Association of the tag SNPs in the human Skt gene (KIAA1217) with lumbar disc herniation. Journal of Bone and Mineral Research. 2009;24:1537–1543