Lee Eun Bong, Zhao Jinying, Kim Jeong Yeon, Xiong Momiao, Song Yeong Wook
Seoul National University, Seoul, Republic of Korea.
Arthritis Rheum. 2007 Jul;56(7):2443-8. doi: 10.1002/art.22742.
To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).
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.
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.
Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.
研究趋化因子途径中的基因多态性，并评估它们与系统性硬化症（SSc）易感性的相互作用。
为了确定趋化因子途径中的基因多态性赋予的SSc风险，在韩国人群中的99例SSc患者和198例年龄及性别匹配的对照中研究了来自8个候选基因的10个单核苷酸多态性（SNP）。通过聚合酶链反应-限制性片段长度多态性或序列特异性引物方法对SNP进行基因分型。使用卡方检验估计每个SNP与SSc风险之间的遗传关联，以比值比及其95%置信区间计算。构建了CCL5（调节激活正常T细胞表达和分泌因子）基因中2个多态性的单倍型，并测试了它们与SSc的关联。使用最近描述的一种新方法研究基因-基因相互作用，并通过条件逻辑回归确认结果。基于Bonferroni校正对多重检验进行调整。
有显著证据表明基因CXCL8（白细胞介素-8）和CCL5中的多态性之间存在基因-基因相互作用，并且这两者均与SSc风险增加相关。这种SNP-SNP相互作用通过2种独立的统计方法得到确认。在对多重检验进行Bonferroni校正后，这些关联仍然显著。未发现每个个体SNP或单倍型与SSc风险之间存在显著关联。
两种趋化因子CXCL8和CCL5之间的相互作用可能导致对SSc的易感性。
