Mangano Valentina D, Clark Taane G, Auburn Sarah, Campino Susana, Diakite Mahamadou, Fry Andrew E, Green Angela, Richardson Anna, Jallow Muminatou, Sisay-Joof Fatou, Pinder Margaret, Griffiths Michael J, Newton Charles, Peshu Norbert, Williams Thomas N, Marsh Kevin, Molyneux Malcolm E, Taylor Terrie E, Modiano David, Kwiatkowski Dominic P, Rockett Kirk A
Childhood Infection Group, The Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
PLoS One. 2009;4(1):e4206. doi: 10.1371/journal.pone.0004206. Epub 2009 Jan 15.
Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria.
干扰素调节因子1（IRF-1）是转录因子IRF家族的成员，在免疫系统的基因调控网络中发挥着关键且多样的作用。IRF-1被认为是γ干扰素信号传导的关键介质，也是驱动TH1型反应的主要参与者。因此，它在针对细胞内病原体（如恶性疟原虫）的先天性和适应性反应中可能都至关重要。先前已发现人类IRF1基因座的多态性与自然暴露于疟疾的人群中控制恶性疟原虫感染的能力有关。为了测试IRF1基因座的遗传变异是否也会影响患重症疟疾的风险，我们利用来自961个三联体（由一名患病儿童及其父母组成，其中555个来自冈比亚，204个来自肯尼亚，202个来自马拉维）的基因型数据，对三个非洲人群中该基因的18个单核苷酸多态性（SNP）进行了基于家系的关联测试。在任何研究人群中，所测试的任何SNP/单倍型均未观察到与重症疟疾或重症疟疾亚表型（脑型疟疾和重症疟疾贫血）有显著关联。我们的结果表明，没有证据表明转录因子IRF-1调控的分子途径参与了重症疟疾基于免疫的发病机制。
