Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis

Arthritis Rheum. 2007 Jul;56(7):2443-8. doi: 10.1002/art.22742.


Objective: To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).

Methods: To identify the risk of SSc conferred by genetic polymorphisms in the chemokine pathway, 10 single-nucleotide polymorphisms (SNPs) from 8 candidate genes were studied in 99 patients with SSc and 198 age- and sex-matched controls in a Korean population. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism or sequence-specific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chi-square tests. Haplotypes for the 2 polymorphisms in the gene CCL5 (RANTES) were constructed, and their associations with SSc were tested. Gene-gene interactions were investigated using a recently described novel method, and the results were confirmed by conditional logistic regression. Adjustment for multiple testing was based on Bonferroni correction.

Results: There was significant evidence of gene-gene interaction between polymorphisms in the genes CXCL8 (interleukin-8) and CCL5, and both of these were associated with an increased risk of SSc. This SNP-SNP interaction was confirmed by 2 independent statistical methods. The associations remained significant after Bonferroni adjustment for multiple testing. No significant association between each individual SNP or haplotype and the risk of SSc was found.

Conclusion: Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CCL5
  • Chemokines / genetics*
  • Chemokines, CC / genetics
  • Genetic Predisposition to Disease*
  • Humans
  • Interleukin-8 / genetics
  • Korea
  • Polymorphism, Single Nucleotide*
  • Reference Values
  • Scleroderma, Systemic / genetics*


  • CCL5 protein, human
  • Chemokine CCL5
  • Chemokines
  • Chemokines, CC
  • Interleukin-8