COL9A1 gene polymorphism is associated with Kashin-Beck disease in a northwest Chinese Han population

PLoS One. 2015 Mar 16;10(3):e0120365. doi: 10.1371/journal.pone.0120365. eCollection 2015.

Abstract

Objective: We sought to determine whether genomic polymorphism in collagen IX genes (COL9A) was associated with Kashin-Beck disease (KBD).

Methods: Twenty seven single nucleotide polymorphisms (SNPs) in COL9AI, COL9A2 and COL9A3 were genotyped in 274 KBD cases and 248 healthy controls using the Sequenom MassARRAY system. Associations between the COL9A polymorphism and KBD risk were detected using an unconditional logistic regression model. Linkage disequilibrium (LD) and haplotypes analysis were performed with the Haploview software.

Results: After Bonferroni correction, the frequency distribution of genotypes in rs6910140 in COL9A1 was significantly different between the KBD and the control groups (X2 = 16.74, df = 2, P = 0.0002). Regression analysis showed that the allele "C" in SNP rs6910140 had a significant protective effect on KBD [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.34-0.70, P = 0.0001]. The frequencies of alleles and genotypes in rs6910140 were significantly different among subjects of different KBD stages (allele: X2 = 7.82, df = 2, P = 0.02, genotype: X2 = 14.81, df = 4, P = 0.005). However, haplotype analysis did not detect any significant association between KBD and COL9A1, COL9A2 and COL9A3.

Conclusions: We observed a significant association between rs6910140 of COL9A1 and KBD, suggesting a role of COL9A1 in the development of KBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Asian People / genetics*
  • Case-Control Studies
  • China / epidemiology
  • Collagen Type IX / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Humans
  • Kashin-Beck Disease / diagnosis
  • Kashin-Beck Disease / epidemiology
  • Kashin-Beck Disease / genetics*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Severity of Illness Index

Substances

  • COL9A1 protein, human
  • COL9A2 protein, human
  • COL9A3 protein, human
  • Collagen Type IX

Grants and funding

This research was supported by grants from the National Natural Science Foundation of China (No. 81273007); The Foundation of Shaanxi Province of China (2011K15-06-05). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.