Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region
Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region
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DOI：
10.1038/sj.gene.6363928
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发表时间：
2002-12-01
影响因子：
5
通讯作者：
Momigliano-Richiardi, P
中科院分区：
文献类型：
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作者：
D'Alfonso, S;Giordano, M;Momigliano-Richiardi, P
许多证据表明，IL 10是系统性红斑狼疮（SLE）易感性的强候选基因。在我们先前报道的研究中，与对照组相比，意大利SLE患者中位于-1100位点的微卫星IL10.G的等位基因（IL10.G-140 bp）显著增加。从这一观察结果开始，我们测试了IL 10.G附近的序列变异是否与SLE更强相关。我们进行了全面的关联研究，包括跨越IL 10基因的5个侧翼和转录区的8.5Kb的26个SNP（其中4个是在本研究中通过DHPLC分析新鉴定的）。通过DNA池方法对意大利患者（205）和对照组（631）进行相关性研究。通过对IL 10周围的7个选定标记进行个体分型来研究单倍型关联。基因、基因型和单倍型频率在患者和对照组中无显著差异。因此，IL 10 G微卫星至今仍是我们人群中唯一与SLE相关的IL 10标记。对所有已发表结果的荟萃分析表明，IL10.G重复序列数在SLE中可能具有直接作用。
Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position - 1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5 flanking and the transcribed region of the IL 10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibilly.