The involvement of ADAMTS-5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration

Abstract

Low back pain is a global health problem in which more than 40% is caused by lumbar intervertebral disc degeneration (LDD). ADAMTS-5 (A disintegrin and metalloproteinase with thrombospondin motifs-5) was shown to be involved in LDD by functional analyses. To identify whether there is an association between ADAMTS-5 and LDD, and what is the contribution of ADAMTS-5 genetic polymorphisms to MD (Mean diffusivity) changes in lumbar IVD (Intervertebral disc). We firstly genotyped selected ADAMTS-5 SNPs (Single nucleotide polymorphisms) in a Chinese Han population. After the primary analyses of allelic, genotypic, and haplotypic association, we performed SNP-SNP interaction analysis. We subsequently genotyped another 50 participants and acquired the corresponding MD values from individual lumbar IVDs. The association analysis between the genotypic groups divided by the above positive SNPs and the corresponding MD values were also performed. Significant associations were identified in rs151058, rs229052, and rs162502. None of the 2-SNP haplotypic analysis survived the 10,000 permutation test. The following interaction analysis demonstrated that rs151058 was strong associated with LDD when conditioning on rs162502. Significant difference of MD values between AA and G+ carriers was identified in rs162502. This is the first study indicating that the SNPs of ADAMTS-5 may contribute to predisposition of LDD. An interaction between rs151058 and rs229052 may exist in ADAMTS-5 with LDD. The rs162502 might be associated with altered MD values.

Keywords: a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5); diffusion tensor imaging (DTI); lumbar disc degeneration (LDD); single nucleotide polymorphism (SNP).