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

Abstract

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 reactionrestriction fragment length polymorphism or sequencespecific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chisquare 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 genegene 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.

Survival of Adults With Systemic Sclerosis Following Lung Transplantation: A Nationwide Cohort Study

“…In addition, several chemokines that have been implicated in the pathogenesis of SSc have been found to be up‐regulated in bronchoalveolar lavage fluid from adults with chronic lung allograft rejection following lung transplantation . These include CXCL8 , CXCL10 , CCL2 , CCL3 , CCL4 , CCL7 , and CCL18 . Thus, adults with SSc may have an increased susceptibility to innate and adaptive immune responses following lung transplantation.…”

An investigation of the inflammatory cytokine and chemokine network in systemic sclerosis

“…There are also a number of reports linking CCL2 polymorphisms with SSc,39 although other studies do not support this association and this remains a controversial issue 40. Other inflammatory chemokines have been associated with SSc, and compound polymorphisms in CCL5 and CXCL8 appear to increase the risk of SSc 41. Thus SSc, like all other inflammatory and immune disorders, results from a significantly chemokine-dependent pathogenesis.…”

Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP

“…22,25 For a multiple regression test for SNPs, we applied permutation tests of haplotype in LD block because the Bonferroni correction is rather conservative and too restrictive. 26,27 RESULTS Allelic and genotype association study.…”