Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis
Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis
复制标题
DOI：
10.1002/art.22742
复制
发表时间：
2007-07-01
影响因子：
--
通讯作者：
Song, Yeong Wook
中科院分区：
文献类型：
--
作者：
Lee, Eun Bong;Zhao, Jinying;Song, Yeong Wook
目标。研究趋化因子途径的遗传多态，并评估它们之间的相互作用与系统性硬化症(SSC)易感性的关系。为了确定趋化因子途径的遗传多态与SSC的风险，对99例SSC患者和198例韩国人年龄和性别匹配的对照进行了8个候选基因的10个单核苷酸多态(SNPs)研究。采用聚合酶链式反应-限制性片段长度多态性或序列特异性引物法进行SNPs基因分型。每个SNP和SSC风险之间的遗传关联，以95%可信区间的优势比计算，使用卡方检验进行评估。构建了CCL5(RANTES)基因2个多态的单倍型，并对其与SSc的相关性进行了检验。用最近描述的一种新方法研究了基因-基因的相互作用，结果用条件Logistic回归得到了证实。根据Bonferroni矫正法对多次试验进行调整。有显著证据表明，CXCL8(白介素8)和CCL5基因的多态之间存在显著的基因-基因交互作用，这两个基因都与SSC的风险增加有关。用两种独立的统计方法证实了SNP-SNP的相互作用。在Bonferroni对多项测试进行调整后，相关性仍然显著。未发现每一个体SNP或单倍型与SSC风险显著相关。趋化因子CXCL8和CCL5之间的串扰可能与SSC的易感性有关。
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 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 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.