Association study of COL9A2 with lumbar disc disease in the Japanese population

J Hum Genet. 2006;51(12):1063-1067. doi: 10.1007/s10038-006-0062-9. Epub 2006 Sep 23.

Abstract

Lumbar disc disease (LDD) is a common musculo-skeletal disease with strong genetic determinants. In a Finnish population, a single nucleotide polymorphism (SNP) causing an amino-acid substitution (Trp2 allele) in COL9A2, which encodes the alpha2 (IX) chain of type IX collagen, has been reported to associate with LDD. However, replication studies in different populations have produced controversial results. To further investigate the association of COL9A2 with LDD in Japanese, we examined SNPs in COL9A2, including Trp2, in 470 LDD patients (mean age 35) along with 658 controls (mean age 48). We identified a total of 43 sequence variations in COL9A2. Nine SNPs, including Trp2, were selected and genotyped. After Bonferroni's correction, none of these SNPs showed association. Unlike observations in the Finnish population, Trp2 was common in Japanese, and no association with LDD was apparent. However, we did see association of a COL9A2 specific haplotype with LDD (P=0.025; permutation test); this association is more significant in patients with severe lumbar disc degeneration (P=0.011). Thus, the association of Trp2 with LDD was not replicated, but COL9A2 susceptibility allele(s) other than Trp2 may be present in Japanese LDD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Alleles
  • Asian People
  • Collagen Type IX / genetics*
  • DNA Mutational Analysis
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Haplotypes
  • Humans
  • Intervertebral Disc*
  • Lumbar Vertebrae*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Spinal Diseases / etiology
  • Spinal Diseases / genetics*
  • Spinal Diseases / pathology
  • Tryptophan / genetics

Substances

  • COL9A2 protein, human
  • Collagen Type IX
  • Tryptophan