IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level
IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level
复制标题
DOI：
10.1007/s10875-008-9197-0
复制
发表时间：
2008-09-01
影响因子：
9.1
通讯作者：
Jurado, M.
中科院分区：
文献类型：
--
作者：
Sainz, J.;Perez, E.;Jurado, M.
目的 本研究的目的是确定白细胞介素 1 α (IL1 α)、白细胞介素 1 β (IL1 β) 和 IL1 受体拮抗剂 (IL1Ra) 多态性是否与侵袭性肺曲霉病 (IPA) 发病机制有关。 材料和方法 受试者包括 110 名血液病患者和 148 名健康对照。血液病患者和对照之间的基因型和等位基因频率相似。根据欧洲癌症研究和治疗组织/侵袭性真菌感染合作组 (EORTC/IFICG) 发布的共识标准，110 名患者中的 59 名被诊断为 IPA。 结果和讨论 个体基因座分析显示 IL1 α 和 IL1Ra 多态性与 IPA 的存在无关（分别为 p=0.560 和 p=0.680）。然而，发现 IPA 组中 IL1 beta(-511TT) 基因型（或 IL1 beta(-511T) 等位基因）存在高于非 IPA 患者组的趋势（分别为 p=0.092 和 p=0.095）。单倍型分析显示，VNTR2/-889C/-511T 单倍型与 IPA 感染的易感性密切相关 (p=0.020)。单倍型分析还显示 VNTR2/-889C/-511C 单倍型与 IPA 感染抗性之间存在关联 (p=0.028)。此外，与其他基因型患者相比，IL1Ra VNTR2/2 和 IL1 beta T-511/T 基因型患者的血清半乳甘露聚糖阳性百分比较高。最后，C 反应蛋白 (CRP) 的产生与 IL1 基因簇多态性显着相关，尽管 IPA 和非 IPA 组之间的 CRP 值相似。 结论 这些发现表明 IL1 基因簇多态性在 IPA 感染和 CRP 产生的易感性中发挥着关键作用。
Objective The aim of this study was to determine whether interleukin-1 alpha (IL1 alpha), interleukin-1 beta (IL1 beta), and IL1 receptor antagonist (IL1Ra) polymorphisms are implicated in invasive pulmonary aspergillosis (IPA) pathogenesis.Materials and Methods Subjects comprised 110 hematological patients and 148 healthy controls. Genotypic and allelic frequencies were similar between hematological patients and controls. IPA was diagnosed in 59 of the 110 patients according to consensus criteria published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/IFICG).Results and Discussions Individual locus analysis showed that IL1 alpha and IL1Ra polymorphisms were not associated with the presence of IPA (p=0.560 and p=0.680, respectively). However, a trend towards a higher presence of IL1 beta(-511TT) genotype (or IL1 beta(-511T) allele) in the IPA group than in the non-IPA patient group (p=0.092 and p=0.095, respectively) was found. Haplotype analysis revealed that VNTR2/-889C/-511T haplotype was strongly associated with susceptibility to develop IPA infection (p=0.020). Haplotype analysis also showed an association between VNTR2/-889C/-511C haplotype and resistance to IPA infection (p=0.028). Furthermore, patients with IL1Ra VNTR2/2 and IL1 beta T-511/T genotypes had a higher positive serum galactomannan percentage versus patients with other genotypes. Finally, C-reactive protein (CRP) production was significantly associated with IL1 gene cluster polymorphisms, although CRP values were similar between IPA and non-IPA groups.Conclusion These findings indicate a critical role of IL1 gene cluster polymorphisms in the susceptibility to IPA infection and CRP production.