在马里的一项队列研究中，非洲中心 S47 或 P72 变体都与降低发热性疟疾的风险无关。
Neither the African-Centric S47 Nor P72 Variant of TP53 Is Associated With Reduced Risk of Febrile Malaria in a Malian Cohort Study.
机构信息
Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Mali International Center of Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
出版信息
J Infect Dis. 2023 Jul 14;228(2):202-211. doi: 10.1093/infdis/jiad066.
BACKGROUND
TP53 has been shown to play a role in inflammatory processes, including malaria. We previously found that p53 attenuates parasite-induced inflammation and predicts clinical protection to Plasmodium falciparum infection in Malian children. Here, we investigated whether p53 codon 47 and 72 polymorphisms are associated with differential risk of P. falciparum infection and uncomplicated malaria in a prospective cohort study of malaria immunity.
METHODS
p53 codon 47 and 72 polymorphisms were determined by sequencing TP53 exon 4 in 631 Malian children and adults enrolled in the Kalifabougou cohort study. The effects of these polymorphisms on the prospective risk of febrile malaria, incident parasitemia, and time to fever after incident parasitemia over 6 months of intense malaria transmission were assessed using Cox proportional hazards models.
RESULTS
Confounders of malaria risk, including age and hemoglobin S or C, were similar between individuals with or without p53 S47 and R72 polymorphisms. Relative to their respective common variants, neither S47 nor R72 was associated with differences in prospective risk of febrile malaria, incident parasitemia, or febrile malaria after parasitemia.
CONCLUSIONS
These findings indicate that p53 codon 47 and 72 polymorphisms are not associated with protection against incident P. falciparum parasitemia or uncomplicated febrile malaria.
背景
TP53 已被证明在炎症过程中发挥作用，包括疟疾。我们之前发现 p53 可减轻寄生虫引起的炎症，并可预测马里儿童感染疟原虫的临床保护作用。在此，我们通过对疟疾免疫的前瞻性队列研究，调查了 p53 密码子 47 和 72 多态性是否与疟原虫感染和无并发症疟疾的风险差异相关。
方法
在卡利法布古队列研究中，对 631 名马里儿童和成年人的 TP53 外显子 4 进行测序，确定 p53 密码子 47 和 72 多态性。使用 Cox 比例风险模型评估这些多态性对 6 个月强烈疟疾传播期间发热性疟疾、新出现的寄生虫血症以及新出现的寄生虫血症后发热时间的前瞻性风险的影响。
结果
疟疾风险的混杂因素，包括年龄和血红蛋白 S 或 C，在具有或不具有 p53 S47 和 R72 多态性的个体之间相似。与各自的常见变体相比，S47 或 R72 均与发热性疟疾、新出现的寄生虫血症或寄生虫血症后的发热性疟疾的前瞻性风险差异无关。
结论
这些发现表明，p53 密码子 47 和 72 多态性与预防疟原虫感染或无并发症发热性疟疾无关。
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