Association of the Tag SNPs in the Human SKT Gene (KIAA1217) With Lumbar Disc Herniation

• DOI: 10.1359/jbmr.090314
• Publication Date: 2009-04-01T15:10:02Z
• Authors: Tatsuki Karasugi; Kei Semba; Yuichiro Hirose; Anthi Kelempisioti; Masahiro Nakajima; Atsushi Miyake; Tatsuya Furuichi; Yoshiharu Kawaguchi; Yasuo Mikami; Kazuhiro Chiba; Michihiro Kamata; Kouichi Ozaki; Atsushi Takahashi; Pirkka Mäkelä; Jaro Karppinen; Tomoatsu Kimura; Toshikazu Kubo; Yoshiaki Toyama; Ken-ichi Yamamura; Minna Männikkö; Hiroshi Mizuta; Shiro Ikegawa
• Keywords: 0301 basic medicine; 03 medical and health sciences; Lumbar Vertebrae; Base Sequence; Case-Control Studies; Humans; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Intervertebral Disc Displacement; DNA Primers

Abstract Lumbar disc herniation (LDH) is one of the most common musculo-skeletal diseases. Recent studies have indicated that LDH has strong genetic determinants, and several susceptibility genes have been reported to associate with LDH; however, its etiology and pathogenesis still remain unclear. KIAA1217 (alias SKT, the human homolog of murine Skt [Sickle tail]) is a good candidate for an LDH susceptibility gene because SKT is specifically expressed in nucleus pulposa of intervertebral discs (IVDs) in humans and mice, and SktGt mice, which are established through a large-scale gene-trap mutagenesis, exhibit progressive, postnatal onset abnormality of the IVDs. Here, we report the association of SKT with LDH. Using tag SNPs, we examined the association in two independent Japanese case-control populations and found a significant association with SKT rs16924573 in the allele frequency model (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). Our data indicate that SKT is involved in the etiology of LDH.