Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.
Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.
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人类白细胞抗原（HLA）变异与特发性肺纤维化的关联研究。
DOI：
10.1101/2023.07.20.23292940
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Guillen-Guio B
中科院分区：
文献类型：
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作者：
Guillen-Guio B
特发性肺纤维化（IPF）是一种以进行性肺纤维化为特征的慢性间质性肺炎，预后不良。最近的研究强调了感染在IPF发病机制中的潜在作用，并报道了HLA-DQB 1基因与特发性纤维化间质性肺炎（包括IPF）的既往相关性。由于人类白细胞抗原（HLA）区域在免疫应答中起重要作用，在此我们评估HLA遗传变异是否与IPF风险特异性相关。MethodsWe对来自7项独立IPF病例对照研究的欧洲血统个体的HLA区域与IPF风险的关联进行了荟萃分析（包括5159例病例和27459例对照，包括纤维化间质性肺炎的既往研究）。分析单核苷酸多态性、经典HLA等位基因和氨基酸，满足p<4.5×10− 4的区域范围关联阈值和后验复制概率>90%的信号被认为是显著的。我们试图复制先前appropriatedHLA-DQB 1协会在独立的原始report.ResultsThe荟萃分析的所有7项研究的子集中确定了4个重要的独立的单核苷酸多态性与IPF的风险。然而，没有一个符合复制标准的后验概率。TheHLA-DQB 1关联在独立的IPF研究中未被复制。结论HLA区域变异与IPF研究中的风险并不一致。然而，这并不排除与免疫应答相关的其他基因组区域可能参与IPF病因的可能性。
IntroductionIdiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of theHLA-DQB1gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk.MethodsWe performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case–control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10−4and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reportedHLA-DQB1association in the subset of studies independent of the original report.ResultsThe meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. TheHLA-DQB1association was not replicated in the independent IPF studies.ConclusionVariation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.