He H, Isnard A, Kouriba B, Cabantous S, Dessein A, Doumbo O, Chevillard C
INSERM, U399, Marseille, France.
Genes Immun. 2008 Apr;9(3):195-206. doi: 10.1038/gene.2008.2. Epub 2008 Feb 14.
Th2-mediated immunity is critical for human defence against schistosome, and susceptibility to infection is controlled by a major genetic locus, mapped on the 5q31-q33 region comprising the genes IL4, IL5 and IL13. We have reported an association between the rs1800925 polymorphism in the IL13 promoter and infection levels in a Dogon population (693 subjects in Ségué and 148 in Boul), where Schistosoma haematobium is endemic. In the same population, we investigated whether other polymorphisms in genes involved in type 2 cytokine immune response could affect susceptibility to schistosome infection. By logistic regression analysis, we found an association between a single-nucleotide polymorphism (SNP) in the STAT6 gene (rs324013) and infection levels (P=0.04). We confirmed this association in analyses restricted to subjects under 20 years age and living in Boul, the village with the highest levels of infection (P=0.005). We detected an additive effect of the rs324013 and rs1800925 polymorphisms (P=0.011). These SNPs were not strongly correlated with any other tested markers surrounding the two genes. Furthermore, electrophoretic mobility shift assay has shown that both polymorphisms affect transcription factor binding. These results are consistent with the Th2 cytokine pathway enhancing resistance to schistosome infection in humans.
Th2介导的免疫对于人类抵御血吸虫至关重要，而感染易感性由一个主要基因位点控制，该位点定位于5q31 - q33区域，包含IL4、IL5和IL13基因。我们曾报道在血吸虫病流行的多贡人群（塞盖有693名受试者，布尔有148名受试者）中，IL13启动子中的rs1800925多态性与感染水平之间存在关联。在同一人群中，我们研究了参与2型细胞因子免疫反应的基因中的其他多态性是否会影响血吸虫感染的易感性。通过逻辑回归分析，我们发现STAT6基因中的一个单核苷酸多态性（SNP，rs324013）与感染水平之间存在关联（P = 0.04）。我们在仅限于20岁以下且生活在感染水平最高的布尔村的受试者的分析中证实了这种关联（P = 0.005）。我们检测到rs324013和rs1800925多态性存在加性效应（P = 0.011）。这些SNP与这两个基因周围的任何其他测试标记均无强相关性。此外，电泳迁移率变动分析表明这两种多态性均影响转录因子结合。这些结果与Th2细胞因子途径增强人类对血吸虫感染的抵抗力是一致的。
