HLA and cytokine gene polymorphisms in biliary atresia
HLA and cytokine gene polymorphisms in biliary atresia
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DOI：
10.1046/j.0106-9543.2002.01647.x
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发表时间：
2002-06-01
期刊：
影响因子：
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通讯作者：
Kelley, D
中科院分区：
文献类型：
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作者：
Donaldson, PT;Clare, M;Kelley, D
背景/目的：肝外胆道闭锁仍然是儿童早期死亡的主要肝脏原因之一。虽然已经提出了一些假说来解释这种疾病，但其病因机制知之甚少。一种可能性是，这是一种免疫介导的疾病，在遗传易感宿主中发生毒性或感染性损伤后发生。早期的研究表明弱HLA协会，但这些仍然未经证实。最近病毒性和自身免疫性肝病的研究已经开始调查非MHC免疫调节基因多态性。研究方法：在本研究中，我们使用分子基因分型调查选定的HLA A，B，DRB 1，DQA 1，DQB 1和DPB 1等位基因，以及白细胞介素-1基因家族，白细胞介素-10启动子序列和肿瘤坏死因子α启动子基因的多态性在101名儿童参考手术评估与肝外胆道闭锁。基因分型数据与134名种族和地理位置匹配的健康成人卫生保健工作者进行了比较。结果与结论：总的来说，比较患者和对照组，任何测试的基因的分布都没有统计学显著差异。这些数据表明，胆道闭锁不是一种HLA相关疾病，白细胞介素-1和白细胞介素-10基因多态性不是这种疾病的危险因素。
Background/Aims: Extrahepatic biliary atresia remains one of the major hepatic causes of death in early childhood. Though a number of hypotheses have been developed to account for this disease, its aetiopathogenesis is poorly understood. One possibility is that this is an immune mediated disease which occurs following either toxic or infectious insult in a genetically susceptible host. Earlier studies suggested weak HLA associations but these remain unconfirmed. More recently studies of viral and autoimmune liver disease have begun to investigate non-MHC immunoregulatory gene polymorphisms. Methods: In the present study we used molecular genotyping to investigate selected HLA A, B, DRB1 , DQA1 , DQB1 and DPB1 alleles as well as polymorphisms in the interleukin-1 gene family, interleukin-10 promoter sequence and tumour necrosis factor alpha promoter genes in 101 children referred for surgical assessment with extra hepatic biliary atresia. Genotyping data were compared with those of 134 racially and geographically matched healthy adult health care workers. Results and conclusions: Overall there were no statistically significant differences in the distribution of any of the genes tested comparing patients and controls. These data suggest that biliary atresia is not an HLA-associated disease and that polymorphisms in both the interleukin-1 and interleukin-10 genes are not risk factors for this disease.