PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever
PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever
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DOI：
10.1111/j.1365-2249.2006.03087.x
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发表时间：
2006-06-01
影响因子：
4.6
通讯作者：
van Dissel, J. T.
中科院分区：
文献类型：
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作者：
Ali, S.;Vollaard, A. M.;van Dissel, J. T.
宿主遗传因素可能与传染病的易感性和结果有关。最近发现，与泛素化和蛋白酶体介导的蛋白质降解相关的基因簇PARK2/PACRG的多态性与麻风分枝杆菌的明显感染有关。在这里，我们研究了这些多态性是否与伤寒沙门菌和副伤寒沙门菌感染的易感性有关，这两种细胞内病原体在人类感染后与分枝杆菌共享宿主的免疫反应。采用聚合酶链反应和限制性内切片段长度多态性方法对印度尼西亚雅加达某流行区伤寒和副伤寒患者的PARK_e01（-697）、PARK2_e01（-2599）、rs1333955和rs1040079的多态性进行分析。在这项研究中，从被动社区监测中血液培养确诊的伤寒（n = 90）、副伤寒（n = 26）和发热对照（n = 337）患者中采集样本，并与来自同一城市地区随机选择的社区对照（n = 322）进行比较。PARK2_e01（-2599）等位基因T与伤寒和副伤寒有显著相关性（OR: 1.51, 95%CI: 1.02 ~ 2.23），而PARK2_e01（-697）、rs1333955和rs1040079等位基因T与伤寒和副伤寒无显著相关性。虽然在PARK2/PACRG基因簇中，PARK2_e01（-2599）等位基因T与麻风病的相关性最强（OR类似于3-5），但与伤寒的相关性要弱得多。我们的研究结果表明，PARK2/PACRG的这种多态性在细胞内病原菌伤寒沙门氏菌和副伤寒沙门氏菌的易感性中起着很小但很重要的作用。
Host genetic factors may contribute to susceptibility to and outcome in infectious diseases. Recently polymorphisms in PARK2/PACRG, a gene cluster linked to ubiquitination and proteasome-mediated protein degradation, were found to be associated with manifest infection by M. leprae. Here, we address whether these polymorphisms are associated with susceptibility to infection with Salmonella typhi and S. paratyphi A, intracellular pathogens that upon infection of humans share with mycobacteria aspects of the hosts' immune response. The polymorphisms of PARK_e01(-697), PARK2_e01(-2599), rs1333955 and rs1040079 were analysed by polymerase chain reaction and restriction fragment length polymorphism in a case-control study of typhoid and paratyphoid fever patients in an endemic area in Jakarta, Indonesia. For this study, samples were obtained from patients with blood culture-confirmed typhoid fever (n = 90), paratyphoid fever (n = 26) and fever controls (n = 337) in a passive, community-based surveillance and compared to those of randomly selected community controls (n = 322) from the same city area. The PARK2_e01(-2599) allele T was significantly associated with typhoid and paratyphoid fever (OR: 1.51, 95%CI: 1.02-2.23) but the other polymorphisms, PARK2_e01(-697), rs1333955 and rs1040079, were not associated. Although within the PARK2/PACRG gene cluster the PARK2_e01(-2599) allele T was most strongly associated with leprosy (OR similar to 3-5), the association with typhoid is much less strong. Our findings suggest that this polymorphism in PARK2/PACRG plays a small but significant role in susceptibility to the intracellular pathogens S. typhi and S. paratyphi.