S-Space College of Medicine/School of Medicine (의과대학/대학원) Immunology (면역학전공) Journal Papers (저널논문_면역학전공)
Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis
- Lee, E. B.; Zhao, J.; Kim, J. Y.; Xiong, M.; Song, Y. W.
- Issue Date
- Arthritis Rheum. 2007 Jul;56(7):2443-8.
- Chemokine CCL5; Chemokines/*genetics; Chemokines, CC/genetics; *Genetic Predisposition to Disease; Humans; Interleukin-8/genetics; Korea; *Polymorphism, Single Nucleotide; Reference Values; Scleroderma, Systemic/*genetics
- 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.
- 0004-3591 (Print)
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