The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility
The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility
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DOI：
10.1126/science.1101160
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发表时间：
2005-03-04
期刊：
影响因子：
56.9
通讯作者：
Ahuja, SK
中科院分区：
文献类型：
--
作者：
Gonzalez, E;Kulkarni, H;Ahuja, SK
尽管未知宿主防御的表型后果，但人类基因组中的节段重复有选择地富集与免疫的基因。我们表明，在包含编码CCL3L1基因（MIP-1Alphap）的分段重复的拷贝数中存在显着的间个体和互插差异，这是一种有效的人免疫缺陷病毒（HIV-1） - 促进性的趋化性趋化剂和配体CCR5。拥有低于人口平均值的CCL3L1拷贝数与艾滋病毒/获得性免疫缺陷综合征（AIDS）敏感性显着相关。在还具有疾病的CCR5基因型的个体中，这种敏感性甚至更大。 CCL3L1剂量与改变HIV/AIDS敏感性之间的这种关系表明CCL3L1在HIV/AIDS发病机理中的核心作用，表明免疫反应基因剂量的差异可能构成对感染性疾病的可变反应的遗传基础。
Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.