Recent evidence suggests that proprotein convertase subtilisin/kexin type 9 (PCSK9), a downmodulator of cellular uptake of blood cholesterol, also negatively impacts host immune response to microbial infection. In this study, we investigated whether carrying the loss-of-function (LOF) rs562556 (c.1420 A > G; p.I474 V) PCSK9 single nucleotide polymorphism (SNP) affected the outcome of severe malaria in children. Archival DNA of a cohort of 207 Malian children suffering from severe malaria was genotyped for the rs562556 SNP. Sixty-four children were either heterozygous or homozygous for the minor G allele (carriers); 143 children were homozygous for the common A allele (noncarriers). Among carriers, there was one mortality case (1.6%), compared to 15 cases (10.5%) among noncarriers (), suggesting that the G allele is associated with better survival in severe malaria. Intriguingly, this allele did not negatively segregate with any of the clinical symptoms linked to mortality in this cohort. Studies are needed to determine whether PCSK9 inactivation promotes a protective immune response to malaria infection.

中文翻译：

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rs562556 PCSK9基因多态性与马里儿童严重疟疾死亡率降低的关系

最近的证据表明，前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）是细胞吸收胆固醇的下调因子，也对宿主对微生物感染的免疫反应产生负面影响。在这项研究中，我们调查了携带功能丧失（LOF）rs562556（c.1420 A> G; p.I474 V）PCSK9单核苷酸多态性（SNP）是否会影响儿童严重疟疾的后果。对rs562556 SNP对207名患有严重疟疾的马里儿童队列的档案DNA进行了基因分型。六十四个孩子的次要G等位基因（携带者）为杂合子或纯合子；143名儿童是普通A等位基因（非携带者）的纯合子。携带者中有1例死亡病例（1.6％），而非携带者中有15例（10.5％）（），表明G等位基因与严重疟疾的较好生存有关。有趣的是，该等位基因并未与该队列中与死亡率相关的任何临床症状阴性分离。需要进行研究以确定PCSK9失活是否促进对疟疾感染的保护性免疫反应。