Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant

You Qiang Song, Tatsuki Karasugi, Kenneth M.C. Cheung, Kazuhiro Chiba, Daniel W.H. Ho, Atsushi Miyake, Patrick Y.P. Kao, Kit Ling Sze, Anita Yee, Atsushi Takahashi, Yoshiharu Kawaguchi, Yasuo Mikami, Morio Matsumoto, Daisuke Togawa, Masahiro Kanayama, Dongquan Shi, Jin Dai, Qing Jiang, Chengai Wu, Wei TianNa Wang, John C.Y. Leong, Keith D.K. Luk, Shea Ping Yip, Stacey S. Cherny, Junwen Wang, Stefan Mundlos, Anthi Kelempisioti, Pasi J. Eskola, Minna Männikkö, Pirkka Mäkelä, Jaro Karppinen, Marjo Riitta Järvelin, Paul F. O'Reilly, Michiaki Kubo, Tomoatsu Kimura, Toshikazu Kubo, Yoshiaki Toyama, Hiroshi Mizuta, Kathryn S.E. Cheah, Tatsuhiko Tsunoda, Pak Chung Sham, Shiro Ikegawa, Danny Chan

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)


Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family-based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.

Original languageEnglish
Pages (from-to)4909-4917
Number of pages9
JournalJournal of Clinical Investigation
Issue number11
Publication statusPublished - 2013 Nov 1

ASJC Scopus subject areas

  • General Medicine


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