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

Cited 19 time in Web of Science Cited 18 time in Scopus
Authors
Lee, E. B.; Zhao, J.; Kim, J. Y.; Xiong, M.; Song, Y. W.
Issue Date
2007-06-30
Publisher
Wiley-Blackwell
Citation
Arthritis Rheum. 2007 Jul;56(7):2443-8.
Keywords
Chemokine CCL5Chemokines/*geneticsChemokines, CC/genetics*Genetic Predisposition to DiseaseHumansInterleukin-8/geneticsKorea*Polymorphism, Single NucleotideReference ValuesScleroderma, Systemic/*genetics
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 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.
ISSN
0004-3591 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17599774

http://hdl.handle.net/10371/22394
DOI
https://doi.org/10.1002/art.22742
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College of Medicine/School of Medicine (의과대학/대학원)Immunology (면역학전공)Journal Papers (저널논문_면역학전공)
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