Mangano V D, Luoni G, Rockett K A, Sirima B S, Konaté A, Forton J, Clark T G, Bancone G, Sadighi Akha E, Kwiatkowski D P, Modiano D
Dipartimento di Scienze di Sanità Pubblica, Sezione di Parassitologia, Università di Roma 'La Sapienza', Rome, Italy.
Genes Immun. 2008 Mar;9(2):122-9. doi: 10.1038/sj.gene.6364456. Epub 2008 Jan 17.
We describe the haplotypic structure of the interferon regulatory factor-1 (IRF-1) locus in two West African ethnic groups, Fulani and Mossi, that differ in their susceptibility and immune response to Plasmodium falciparum malaria. Both populations showed significant associations between IRF-1 polymorphisms and carriage of P. falciparum infection, with different patterns of association that may reflect their different haplotypic architecture. Genetic variation at this locus does not therefore account for the Fulani-specific resistance to malaria while it could contribute to parasite clearance's ability in populations living in endemic areas. We then conducted a case-control study of three haplotype-tagging single nucleotide polymorphisms (htSNPs) in 370 hospitalised malaria patients (160 severe and 210 uncomplicated) and 410 healthy population controls, all from the Mossi ethnic group. All three htSNPs showed correlation with blood infection levels in malaria patients, and the rs10065633 polymorphism was associated with severe disease (P=0.02). These findings provide the first evidence of the involvement in malaria susceptibility of a specific locus within the 5q31 region, previously shown to be linked with P. falciparum infection levels.
我们描述了富拉尼族和莫西族这两个西非族群中干扰素调节因子-1（IRF-1）基因座的单倍型结构，这两个族群对恶性疟原虫疟疾的易感性和免疫反应有所不同。两个族群均显示出IRF-1多态性与恶性疟原虫感染携带之间存在显著关联，且关联模式不同，这可能反映了它们不同的单倍型结构。因此，该基因座的遗传变异并不能解释富拉尼族对疟疾的特异性抗性，不过它可能有助于生活在疟疾流行地区人群清除寄生虫的能力。然后，我们对来自莫西族的370名住院疟疾患者（160名重症患者和210名非重症患者）和410名健康人群对照进行了一项关于三个单倍型标签单核苷酸多态性（htSNP）的病例对照研究。所有三个htSNP均与疟疾患者的血液感染水平相关，且rs10065633多态性与重症疾病相关（P = 0.02）。这些发现首次证明了5q31区域内一个特定基因座参与了疟疾易感性，该区域先前已被证明与恶性疟原虫感染水平有关。
