Polymorphism of the cytokine genes in hospitalized patients with Puumala hantavirus infection
Polymorphism of the cytokine genes in hospitalized patients with Puumala hantavirus infection
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DOI：
10.1093/ndt/16.7.1368
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发表时间：
2001-07-01
影响因子：
6.1
通讯作者：
Pasternack, A
中科院分区：
文献类型：
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作者：
Mäkelä, S;Hurme, M;Pasternack, A
背景肾病综合征（NE）是一种由普马拉（PUU）汉坦病毒引起的轻度肾综合征出血热。NE的临床病程从无症状到致命不等。本研究的目的是确定细胞因子基因的多态性是否与NE的易感性和预后相关。采用聚合酶链反应对87例血清学确诊的急性NE患者进行肿瘤坏死因子α（TNF α）、白细胞介素-1 α（IL-1 α）、IL-1 β和IL-1受体拮抗剂（IL-1 IRA）基因型分析。对照组为400名健康献血员。这400例对照中有19例（5%）为PUU病毒血清阳性。IL-1 β（-511位点碱基交换多态性）等位基因2与IL-1 IRA等位基因2在两组中均存在强相关性。NE患者比PUU-血清阴性献血者更常为IL-1 IRA-2阴性/IL-1 β-2阴性（38 vs 27%比值比1.65，95%置信区间1.0-2.7）。但IL-1 β-2/IL-1-IRA-2阴性患者与其他患者之间NE的临床严重程度无差异。其他等位基因频率研究表明，各组之间没有统计学显著差异。87例患者中有33例（38%）和381例血清阴性对照中有121例（32%）为高产基因型TNF 2等位基因携带者。结论：IL-1 β（-511）等位基因2和IL-1 IRA等位基因2的缺失可能与NE的易感性有关。此外，TNF α多态性似乎与NE的结果相关。
Background. Nephropathia epidemica (NE) is a mild type of haemorrhagic fever with renal syndrome caused by Puumala (PUU) hantavirus. The clinical course of NE varies from asymptomatic to fatal. The aim of this study was to establish whether polymorphisms in the cytokine genes are associated with susceptibility to and outcome of NE.Methods. The genotypes of the genes of tumour necrosis factor alpha (TNFa alpha), interleukin-1 alpha (IL-1 alpha), lL-1 beta and IL-1 receptor antagonist (IL-IRA) were analysed by polymerase chain reaction in 87 subjects, ail hospital-treated for serologically confirmed acute NE. The control group comprised 400 healthy blood donors. Nineteen out of these 400 (5%) controls were PUU virus-seropositive,Results. IL-IRA allele 2 and IL-1 beta (base exchange polymorphism at position -511) allele 2 were strongly associated with each other in both groups. NE patients were more often IL-IRA-2 negative/IL-1 beta -2 negative than PUU-seronegative blood donors (38 vs 27% odds ratio 1.65, 95% confidence interval 1.0-2.7). However there were no differences in the clinical severity of NE between the IL-IRA-2 negative/IL-1 beta -2 negative and the other patients. The other allele frequencies: studied evinced no statistically significant differences between the groups. Thirty-three out of 87 (38%) patients: and 121 out of 381 (32%) seronegative controls were carriers of the high-producer genotype TNF2 allele. Several parameters showed the clinical course of NE to be more severe in TNF2 carriers than in non-carriers.Conclusions, These data suggest that non-carriage of the IL-IRA allele 2 and IL-1 beta (-511) allele 2 may contribute to susceptibility to NE. Furthermore, TNF alpha polymorphism seems to be associated with the outcome of NE.