苏丹内脏利什曼病的遗传易感性：与IL4和IFNGR1的连锁及关联
Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1.
作者信息
Mohamed H S, Ibrahim M E, Miller E N, Peacock C S, Khalil E A G, Cordell H J, Howson J M M, El Hassan A M, Bereir R E H, Blackwell J M
机构信息
Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
出版信息
Genes Immun. 2003 Jul;4(5):351-5. doi: 10.1038/sj.gene.6363977.
Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important. To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P=0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P=0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P=0.031) and associated (P=0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.
苏丹的纵向研究表明，与杜氏利什曼原虫相关的发病率和临床表型存在种族差异。在免疫学上，1型与2型细胞因子反应的偏差很重要。为了确定IL4/IL9或IFNGR1基因多态性是否与易感性有关，我们研究了59个内脏利什曼病（VL）的多病例家庭，这些家庭有或没有黑热病后皮肤利什曼病（PKDL）。多点非参数分析（Allegro）将IL4/IL9与VL本身联系起来（P=0.002）。使用稳健方差估计的传递不平衡检验证实，在VL本身与IL4之间存在连锁关系时存在关联（P=0.008），但与IL9无关联。逐步逻辑回归分析表明，IL4RP2和IL4RP1标记均对该关联有显著贡献，提示存在一种常见的疾病相关单倍型。相比之下，IFNGR1与PKDL存在连锁关系（P=0.031）和关联（P=0.007），但与VL或VL本身无关。因此，2型细胞因子基因的多态性影响VL的潜在易感性，而IFNGR1则与PKDL的易感性特异性相关。
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