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.
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.
Authors: Erin F Gillespie; Konstantinos I Papageorgiou; Roshini Fernando; Nupur Raychaudhuri; Kimberly P Cockerham; Laya K Charara; Allan C P Goncalves; Shuang-Xia Zhao; Anna Ginter; Ying Lu; Terry J Smith; Raymond S Douglas Journal: J Clin Endocrinol Metab Date: 2012-03-07 Impact factor: 5.958
Authors: Zdenka Navratilova; Jozef Lukac; Frantisek Mrazek; Eva Kriegova; Maria Bucova; Vladimir Bosak; Martin Petrek Journal: Mediators Inflamm Date: 2008 Impact factor: 4.711
Authors: Katrin Schmidt; Lorena Martinez-Gamboa; Susan Meier; Christian Witt; Christian Meisel; Leif G Hanitsch; Mike O Becker; Doerte Huscher; Gerd R Burmester; Gabriela Riemekasten Journal: Arthritis Res Ther Date: 2009-07-17 Impact factor: 5.156