Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Department of Medicine, Nijmegen, The Netherlands.
Innate Immun. 2012 Jun;18(3):492-502. doi: 10.1177/1753425911423043. Epub 2011 Oct 12.
Infectious diseases exert a constant evolutionary pressure on the innate immunity genes. TLR4, an important member of the TLR family, specifically recognizes conserved structures of various infectious pathogens. Two functional TLR4 polymorphisms, Asp299Gly and Thr399Ile, modulate innate host defense against infections, and their prevalence between various populations has been proposed to be influenced by local infectious pressures. If this assumption is true, strong local infectious pressures would lead to a homogeneous pattern of these ancient TLR4 polymorphisms in geographically-close populations, while a weak selection or genetic drift may result in a diverse pattern. We evaluated TLR4 polymorphisms in 15 ethnic groups in Iran, to assess whether infections exerted selective pressures on different haplotypes containing these variants. The Iranian subpopulations displayed a heterogeneous pattern of TLR4 polymorphisms, comprising various percentages of Asp299Gly and Thr399Ile, alone or in combination. The Iranian sample, as a whole, showed an intermediate mixed pattern when compared with commonly-found patterns in Africa, Europe, Eastern Asia and the Americas. These findings suggest a weak, or absent, selection pressure on TLR4 polymorphisms in the Middle-East that does not support the assumption of an important role of these polymorphisms in the host defense against local pathogens.
传染病对先天免疫基因施加持续的进化压力。TLR4 是 TLR 家族的重要成员，它特异性地识别各种传染性病原体的保守结构。两种功能性 TLR4 多态性，Asp299Gly 和 Thr399Ile，调节对感染的先天宿主防御，并且它们在不同人群中的流行率被认为受到当地感染压力的影响。如果这一假设是正确的，那么强烈的局部感染压力将导致在地理上接近的人群中这些古老的 TLR4 多态性具有同质模式，而较弱的选择或遗传漂变可能导致多样化的模式。我们评估了伊朗 15 个族群中的 TLR4 多态性，以评估感染是否对包含这些变体的不同单倍型施加了选择性压力。TLR4 多态性在伊朗亚群中表现出异质模式，单独或组合存在不同比例的 Asp299Gly 和 Thr399Ile。与非洲、欧洲、东亚和美洲常见的模式相比，整个伊朗样本显示出中间混合模式。这些发现表明，中东地区对 TLR4 多态性的选择压力较弱或不存在，这并不支持这些多态性在宿主防御局部病原体中起重要作用的假设。
