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标题: PNAS：患者体内基因变异在HIV病毒载量中起重要作用 [打印本页]

作者: ipsvirus 时间: 2015-11-13 15:10
标题: PNAS：患者体内基因变异在HIV病毒载量中起重要作用

近日，大型国际研究小组进行了一项研究，他们在感染了艾滋病毒的患者体中发现了遗传变异对HIV病毒载量有一定的影响。他们所撰写的论文发表在《美国国家科学院院刊》上，并且研究小组描述了研究结果，他们相信未来需要对艾滋病做些什么。

当然，HIV是导致艾滋病的病毒，虽然在过去的几十年里已经有了非常多的讯息了解它，但是现在研究人员仍然需要做更多的研究并且找到合适的方法来治愈它。在这个新的研究项目中，研究人员如果找出基因变异部分就能认为感染了该病的病人所承载的病毒量有所不同。

负载水平指的是给定样本的血液中所发现的艾滋病病毒数量，病人体内低水平艾滋病毒含量通常表明病人免疫系统正在进行激烈的战斗，而高水平的艾滋病毒含量则通常相反。艾滋病病毒载量在个体之间由于遗传、环境和其他因素的不同而数量不同。

为了隔离相关的基因变异，研究人员对7468名艾滋病患者进行了相关研究，这些患者参加了八个不同的艾滋病毒研究，研究者从中获得了他们的健康相关资讯。其中，有6315人有病毒载量设置数据点，这样就能够用于该项研究。为了找到变异点，研究小组研究了800万个病毒变种，他们因此发现了两个重要的变异体，一个在MHC区域的6号染色体上，另一个在CCR区域3号染色体上。

后续的测试表明，大约有12.3%的病毒设定值的变化可以归因于MHC的变体和2.2%的CCR区。他们为了进一步考虑全基因组重要信号而缩小了这一比例，只留下了5%的变异体。

来源：生物谷

作者: ipsvirus 时间: 2015-11-13 15:11
Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.

McLaren PJ1, Coulonges C2, Bartha I1, Lenz TL3, Deutsch AJ4, Bashirova A5, Buchbinder S6, Carrington MN7, Cossarizza A8, Dalmau J9, De Luca A10, Goedert JJ11, Gurdasani D12, Haas DW13, Herbeck JT14, Johnson EO15, Kirk GD16, Lambotte O17, Luo M18, Mallal S19, van Manen D20, Martinez-Picado J21, Meyer L22, Miro JM23, Mullins JI24, Obel N25, Poli G26, Sandhu MS12, Schuitemaker H20, Shea PR27, Theodorou I28, Walker BD29, Weintrob AC30, Winkler CA31, Wolinsky SM32, Raychaudhuri S33, Goldstein DB27, Telenti A34, de Bakker PI35, Zagury JF2, Fellay J36.

Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward.

http://www.pnas.org/content/early/2015/11/04/1514867112.long

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