Association of the asporin D14 allele with lumbar-disc degeneration in Asians

Abstract

Lumbar-disc degeneration (LDD) is a polygenic disease. Susceptibility genes reported so far are mainly extracellular matrix proteins. D14 allele of asporin (ASPN) is associated with osteoarthritis (OA). Candidate-gene association studies showed that the D14 allele is also significantly associated with LDD in Chinese and Japanese individuals. Meta-analysis showed that individuals harboring a D14 allele had higher risk with a summary odds ratio of 1.70 (p = 0.000013). ASPN expression in vertebral discs increased with age and degeneration. Our results indicate ASPN is a LDD gene in Asians, and common risk factors may be considered for OA and LDD.

Figure 1

Expression of ASPN, COL2A1, AGC1, and TGF-β1 in Normal and LDD Discs (A) Relative expression levels of ASPN, COL2A1, and AGC1 in disc cells from microarray analysis with the CODELINK plateform. (B) Dot plots of real-time RT-PCR analysis of ASPN, COL2A1, and AGC1 expression in normal (n = 4, age 16–39) and LDD tissues (n = 4, age 21–49). The bar represents the average value in each group. A p value is given for a statistical difference between normal and LDD groups, and n.s. denotes nonsignificance. (C) ASPN in situ hybridization. (D and E) Immunostaining of (D) ASPN and (E) TGF-β1, in “normal” nondegenerative (35-year-old) and LDD (40-year-old) disc tissues. The following abbreviations are used: AF, annulus fibrosus; NP, nucleus pulposus; and EP, end plate.