Garcia A, Marquet S, Bucheton B, Hillaire D, Cot M, Fievet N, Dessein A J, Abel L
Institut Francais de Recherche Scientifique pour le Developpement en Cooperation (ORSTOM), Organisation de Coordination pour la Lutte Contre les Endemies en Afrique Centrale, Yaoundé, Cameroon.
Am J Trop Med Hyg. 1998 Jun;58(6):705-9. doi: 10.4269/ajtmh.1998.58.705.
There is accumulating evidence for the involvement of genetic factors in the human response to malaria infection, mostly based on results obtained in studies of severe clinical malaria. The role of major gene(s) controlling blood parasitemia levels in human malaria has also been detected by means of segregation analysis. To confirm and to localize such gene(s), we performed a sib-pair linkage analysis investigating the role of five candidate chromosomal regions: 6p21 (HLA-tumor necrosis factor region), 2q13-q21 (genes coding for interleukin-1 alpha and beta), 14q11 (locus coding for the alpha chain of T cell antigen receptor), 7q35 (gene cluster for the beta subunit of T cell receptor), and 5q31-q33, which includes several candidate genes and was recently linked to a locus controlling infection levels by Schistosoma mansoni, denoted as SM1. The analysis was carried out on nine families from a southern Cameroon village, and the phenotype under study was blood infection levels with Plasmodium falciparum. No linkage was found with any of the four markers outside the 5q31-q33 region. A trend in favor of linkage was observed in the distal part of the 5q31-q33 region, especially with the marker D5S636 (P < 0.05 using the Monte Carlo P value), which was the marker that provided the highest evidence for linkage with SM1. These results suggest that a locus influencing P. falciparum levels in malaria could be located in the same genetic region as that containing SM1, indicating that the 5q31-q33 region may be critical in the control of different parasite infections.
越来越多的证据表明，遗传因素参与了人类对疟疾感染的反应，这主要基于重症临床疟疾研究所得出的结果。通过分离分析，还检测到了控制人类疟疾血中疟原虫血症水平的主要基因的作用。为了确认并定位此类基因，我们进行了同胞对连锁分析，研究五个候选染色体区域的作用：6p21（HLA - 肿瘤坏死因子区域）、2q13 - q21（编码白细胞介素 - 1α和β的基因）、14q11（编码T细胞抗原受体α链的基因座）、7q35（T细胞受体β亚基的基因簇）以及5q31 - q33，该区域包含几个候选基因，并且最近与一个控制曼氏血吸虫感染水平的基因座（记为SM1）相关联。分析是在喀麦隆南部一个村庄的九个家庭中进行的，所研究的表型是恶性疟原虫的血液感染水平。在5q31 - q33区域之外的四个标记中未发现连锁关系。在5q31 - q33区域的远端观察到了有利于连锁的趋势，特别是与标记D5S636（使用蒙特卡罗P值时P < 0.05），该标记为与SM1连锁提供了最高证据。这些结果表明，影响疟疾中恶性疟原虫水平的一个基因座可能位于与包含SM1的基因区域相同的位置，这表明5q31 - q33区域可能在控制不同寄生虫感染中起关键作用。
