Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r² = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.

编码 III 型干扰素的IFNL3 / IFNL4基因组区域内的遗传多态性与丙型肝炎病毒的清除密切相关。我们假设 III 型干扰素可能对其他病原体的免疫反应也很重要。在一组 914 名马里儿童中，我们对功能变异体IFNL4 -rs368234815、IFNL4 -rs117648444 和IFNL3 进行了基因分型-rs4803217 并分析了从出生到 5 岁期间 30,626 次门诊就诊记录的疟疾、胃肠道和呼吸道感染事件。与具有 rs368234815-TT/TT 基因型 (IFN-λ4-Null) 的儿童相比，rs368234815-dG 等位基因与较早的胃肠道感染首次发作时间相关性最强 ( p  = 0.003)。rs368234815-dG 等位基因在随访期间发生感染的风险也显着增加，OR = 1.53, 95%CI (1.13–2.07)，胃肠道感染p  = 0.005，OR = 1.30, 95%CI (1.02–1.65)，疟疾p  = 0.033。适度链接的 rs4803217 ( r ² = 此组中的 0.78）在针对 rs368234815 进行调整后较弱且失去意义。我们还分析了与 IFN-λ4 - P70S 组相关的所有结果。我们的结果表明 IFN-λ4 而不是 IFN-λ3 是遗传关联的主要功能性原因，与整体风险增加和首次临床发作时年龄较小，但与几种常见儿科感染的复发或强度无关。