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亲环素A基因调控区域的多态性影响HIV-1感染的易感性。

Polymorphisms in the regulatory region of the Cyclophilin A gene influence the susceptibility for HIV-1 infection.

作者信息

Rits Maarten A N, van Dort Karel A, Kootstra Neeltje A

机构信息

Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

PLoS One. 2008;3(12):e3975. doi: 10.1371/journal.pone.0003975. Epub 2008 Dec 18.

DOI:10.1371/journal.pone.0003975
PMID:19092998
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2599883/
Abstract

BACKGROUND

Previous studies have demonstrated an association between polymorphisms in the regulatory regions of Cyclophilin A (CypA) and susceptibility to both HIV-1 infection and disease progression. Here we studied whether these polymorphisms are associated with susceptibility to HIV-1 infection and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS) in a group of men having sex with men (MSM) and drug users (DU).

METHODOLOGY/PRINCIPAL FINDINGS: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the clinical course of infection in MSM of the ACS. Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

CONCLUSION/SIGNIFICANCE: The results obtained in this study suggest that the A1650G polymorphism in the regulatory region of the CypA gene may be associated with protection from HIV-1 infection, while the 1604G allele may have a weak association with the clinical course of infection in DU.

摘要

背景

先前的研究表明，亲环素A（CypA）调控区的多态性与HIV-1感染易感性及疾病进展之间存在关联。在此，我们研究了这些多态性是否与阿姆斯特丹HIV-1感染与艾滋病队列研究（ACS）中男男性行为者（MSM）和吸毒者（DU）群体的HIV-1感染易感性及疾病进展相关。

方法/主要发现：我们对ACS参与者进行了CypA调控区C1604G和A1650G多态性的筛查。高危血清阴性MSM中1650G等位基因的患病率显著高于HIV-1感染的MSM。然而，C1604G或A1650G与ACS中MSM的感染临床进程无关。有趣的是，当以血浆中每毫升病毒RNA载量高于10（4.5）拷贝作为生存分析的终点时，携带1604G等位基因的ACS-DU参与者显示出显著加速的疾病进展。

结论/意义：本研究结果表明，CypA基因调控区的A1650G多态性可能与预防HIV-1感染有关，而1604G等位基因可能与DU的感染临床进程存在弱关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f24/2599883/1e9b72e707b5/pone.0003975.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f24/2599883/054f73fd1eeb/pone.0003975.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f24/2599883/804491cd97bd/pone.0003975.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f24/2599883/1e9b72e707b5/pone.0003975.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f24/2599883/054f73fd1eeb/pone.0003975.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f24/2599883/804491cd97bd/pone.0003975.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f24/2599883/1e9b72e707b5/pone.0003975.g003.jpg

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