DC-SIGN and DC-SIGNR genetic diversity among different ethnic populations: potential implications for pathogen recognition and disease susceptibility.
DC-SIGN and DC-SIGNR genetic diversity among different ethnic populations: potential implications for pathogen recognition and disease susceptibility.
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DOI：
10.1016/j.humimm.2007.02.002
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发表时间：
2007-06
期刊：
影响因子：
2.7
通讯作者：
Roger M
中科院分区：
文献类型：
--
作者：
Boily-Larouche G;Zijenah LS;Mbizvo M;Ward BJ;Roger M
树突状细胞特异性细胞内黏附分子-3抓取非整合素(DC-SIGN)和DC-SIGNR均为C型凝集素，既可作为细胞黏附受体，又可作为病原体识别受体。由于这些分子在免疫应答中的重要作用，它们的等位基因在人类疾病状态中的意义，以及这些基因座在不同种族人群中可能存在的遗传变异，我们开展了一项研究，以全面分析高加索加拿大人和非洲土著人群中DC-SIGN和DC-SIGNR的多态性。我们报道了几个新的核苷酸变异，它们位于基因的5‘和3’非翻译区，可以影响它们的转录和翻译。DC-SIGN和DC-SIGNR等位基因在非洲人群和非非洲人群中的分布存在显著差异。最后，我们的研究清楚地表明，非洲人在这两个密切相关的免疫位点上表现出比在其他主要人群中观察到的更大的遗传多样性。这些差异可能反映了环境因素产生的进化压力，例如这些地理上不同地区的流行病原体。还需要进一步的研究来确定DC-SIGN和DC-SIGNR基因变异对蛋白质表达、翻译和功能的净影响，并了解这些功能多态如何影响免疫反应或免疫逃逸。
Dendritic cell–specific intracellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN) and DC-SIGNR are C-type lectins that serve both as cell adhesion and pathogen recognition receptors. Because of the essential role of the these molecules in the immune response, the implication of their alleles in human disease states, and the possible genetic variation at these loci among ethnically diverse populations, we undertook a study to analyze the full extent of DC-SIGN and DC-SIGNR polymorphisms in Caucasian Canadian and indigenous African populations. We report several novel nucleotide variants within regulatory 5′- and 3′-untranslated regions of the genes that could affect their transcription and translation. There were significant differences in the distribution of DC-SIGN and DC-SIGNR alleles among African and non-African populations. Finally, our study clearly demonstrates that Africans show greater genetic diversity at these two closely-related immune loci than observed in other major population groups. The differences may reflect evolutionary pressures generated by environmental factors, such as prevalent pathogens in these geographically distinct regions. Further studies will be needed to determine the net impact of DC-SIGN and DC-SIGNR genetic variants on the expression, translation, and function of the proteins and to understand how these functional polymorphisms may affect immune responses or immune escape.
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