Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (IFNL4-dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia. The negative selection of IFNL4-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case-control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6-9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.

中文翻译：

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东非 IFNL4 基因型和儿童伯基特淋巴瘤的风险。

干扰素 lambda 4 (IFN-λ4) 是一种新型 III 型干扰素，只能由 IFNL4 基因第一个外显子内的遗传变异 rs368234815-dG 的携带者表达。基因上无法产生 IFN-λ4（rs368234815-TT/TT 基因型携带者）与丙型肝炎病毒 (HCV) 感染清除率的提高有关。表达 IFN-λ4 的 rs368234815-dG 等位基因 (IFNL4-dG) 在西撒哈拉以南非洲 (SSA) 最常见（高达 78%），而欧洲人和东亚人的这一比例为 35% 和 5%。非洲以外地区 IFNL4-dG 的负选择表明，其保留在非洲人群中可能会带来生存益处，最有可能对儿童而言。为了探讨这一假设，我们对 IFNL4 基因型与儿童伯基特淋巴瘤 (BL) 的风险进行了全面的关联分析，伯基特淋巴瘤是 SSA 中最常见的一种致命感染相关癌症。我们使用了来自东非儿童和未成年人伯基特淋巴瘤流行病学 (EMBLEM) 以及马拉维感染和儿童癌症病例对照研究的 4,038 名儿童的遗传、流行病学和临床数据。广义线性混合模型符合控制年龄、性别、国家/地区、恶性疟原虫感染状态、人群分层和相关性的 Logit 关联，发现 BL 风险与 IFNL4 内的 3 个编码遗传变异（rs368234815、rs117648444 和 rs142981501）之间没有显着关联。以及它们的组合。由于 BL 发生在从早期儿童感染中幸存下来的 6-9 岁儿童中，因此我们的结果表明，应进行更多研究探讨 IFNL4-dG 等位基因在年幼儿童中的关联。这项综合研究为确定 IFN-λ4 对非洲人群的健康影响奠定了重要基础。