CR1 Knops blood group alleles are not associated with severe malaria in the Gambia.
CR1 Knops blood group alleles are not associated with severe malaria in the Gambia.
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CR1 Knops 血型等位基因与冈比亚的严重疟疾无关。
DOI：
10.1038/sj.gene.6363980
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发表时间：
2003
影响因子：
5
通讯作者：
Hill,AVS
中科院分区：
文献类型：
--
作者：
Zimmerman,PA;Fitness,J;Moulds,JM;McNamara,DT;Kasehagen,LJ;Rowe,JAlexandra;Hill,AVS
Knops血型抗原红细胞多态性与基于恶性疟疾的体外玫瑰花结形成（假定的疟疾毒力因子）减少有关。先前已确定的单核苷酸多态性（SNP）在人类补体受体1（CR 1/CD 35）基因的Knops对立抗原S11/S12和McC a/McC B的基础上，我们现在已经进行了基因型比较，以测试这两个分子变异和严重疟疾之间的关联在西非儿童生活在冈比亚。而与S1相关的SNP：Sl 2和McC（B+）在患有严重疟疾的疟疾感染儿童和未感染疟疾寄生虫的对照儿童中分布均匀，观察到Sl 2（0.800，1365/1706）和McC（B+）的高等位基因频率（0.385，658/1706）。此外，当与在所有人群中观察到的Sl 1/McC a等位基因相比时，非洲Sl 2/McC B等位基因似乎是由于正选择而进化的（改良的Nei-Gojobori检验Ka− Ks/se= 1.77，P值< 0.05）。考虑到CR 1在宿主防御中的作用，我们的发现表明，S12和McC B已经出现以赋予针对感染性疾病的选择性优势，鉴于这些病例对照研究数据，感染性疾病不仅仅是恶性疟原虫疟疾。S12和McC B与严重疟疾之间缺乏关联的潜在因素可能涉及CR 1表达水平的变化。
The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC a/McC b, we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl: 2 and McC (b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1365/1706) and McC b (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC a allele observed in all populations, the African Sl 2/McC b allele appears to have evolved as a result of positive selection (modified Nei–Gojobori test Ka− Ks/se= 1.77, P-value< 0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC b have arisen to confer a selective advantage against infectious disease that, in view of these case–control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC b with severe malaria may involve variation in CR1 expression levels.