IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study.
IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study.
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DOI：
10.1007/s00251-012-0604-6
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发表时间：
2012-05
期刊：
影响因子：
3.2
通讯作者：
Grutters, Jan C.
中科院分区：
文献类型：
--
作者：
Korthagen, Nicoline M.;van Moorsel, Coline H. M.;Kazemier, Karin M.;Ruven, Henk J. T.;Grutters, Jan C.
关键词：
特发性肺纤维化（IPF）是一种病因不明的罕见的破坏性肺部疾病。编码白介素-1受体拮抗剂（IL-1Ra）的IL1RN基因的遗传变异与IPF易感性有关。一些研究调查了可变数目串联重复序列（VNTR）或单核苷酸多态性rs408392、rs419598和rs2637988，结果不一。本研究的目的是阐明IL1RN多态性对IPF易感性和mRNA表达的影响。我们对调查白种人IPF中IL1RN多态性的五项病例对照研究进行了荟萃分析。此外，我们还研究了IL1RN多态性是否会影响IL1RN mRNA的表达。VNTR、rs408392和rs419598处于紧密连锁不平衡状态，D值为0.99。rs2637988与VNTR存在连锁不平衡（D′= 0.90）。构建了VNTR*2与rs408392和rs419598等位基因的单位块。meta分析显示，该VNTR*2单倍体块与IPF易感性存在等位基因模型（优势比为1.42,p = 0.002）和携带者模型（优势比为1.60,p = 0.002）相关。rs2637988对IL1RN mRNA的表达有显著影响，（次要）GG基因型携带者的表达水平较低（p < 0.001）。从这项荟萃分析中，我们得出结论，VNTR*2单倍体块与IPF易感性相关。此外，IL1RN的多态性影响IL-1Ra mRNA的表达，表明IL-1Ra水平较低易发生IPF。总之，这些发现表明细胞因子IL-1Ra在IPF发病机制中起作用。
Idiopathic pulmonary fibrosis (IPF) is a rare and devastating lung disease of unknown aetiology. Genetic variations in the IL1RN gene, encoding the interleukin-1 receptor antagonist (IL-1Ra), have been associated with IPF susceptibility. Several studies investigated the variable number tandem repeat (VNTR) or single nucleotide polymorphisms rs408392, rs419598 and rs2637988, with variable results. The aim of this study was to elucidate the influence of polymorphisms in IL1RN on IPF susceptibility and mRNA expression. We performed a meta-analysis of the five case–control studies that investigated an IL1RN polymorphism in IPF in a Caucasian population. In addition, we investigated whether IL1RN mRNA expression was influenced by IL1RN polymorphisms. The VNTR, rs408392 and rs419598 were in tight linkage disequilibrium, with D′ > 0.99. Furthermore, rs2637988 was in linkage disequilibrium with the VNTR (D′ = 0.90). A haploblock of VNTR*2 and the minor alleles of rs408392and rs419598 was constructed. Meta-analysis revealed that this VNTR*2 haploblock is associated with IPF susceptibility both with an allelic model (odds ratio = 1.42, p = 0.002) and a carriership model (odds ratio = 1.60, p = 0.002). IL1RN mRNA expression was significantly influenced by rs2637988, with lower levels found in carriers of the (minor) GG genotype (p < 0.001). From this meta-analysis, we conclude that the VNTR*2 haploblock is associated with susceptibility to IPF. In addition, polymorphisms in IL1RN influence IL-1Ra mRNA expression, suggesting that lower levels of IL-1Ra predispose to developing IPF. Together these findings demonstrate that the cytokine IL-1Ra plays a role in IPF pathogenesis.
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影响因子：
10
作者：
Mapel, DW;Hunt, WC;Coultas, DB
通讯作者：
Coultas, DB
影响因子：
4.6
作者：
Ludwiczek, O;Vannier, E;Tilg, H
通讯作者：
Tilg, H
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
di Giovine, FS
DOI：
10.1164/rccm.200602-163oc
发表时间：
2006-10-01
影响因子：
24.7
作者：
Raghu, Ganesh;Weycker, Derek;Oster, Gerry
通讯作者：
Oster, Gerry