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趋化因子受体CCR2b 64I多态性及其与丹麦HIV感染人群队列中CD4 T细胞计数和疾病进展的关系。哥本哈根艾滋病队列。

Chemokine receptor CCR2b 64I polymorphism and its relation to CD4 T-cell counts and disease progression in a Danish cohort of HIV-infected individuals. Copenhagen AIDS cohort.

作者信息

Eugen-Olsen J, Iversen A K, Benfield T L, Koppelhus U, Garred P

机构信息

Department of Infectious Diseases, Copenhagen University Hospitals, Hvidovre, Denmark.

出版信息

J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Jun 1;18(2):110-6. doi: 10.1097/00042560-199806010-00002.

Abstract

We have investigated the role of the recently described mutation in CCR2b named 64I in relation to HIV resistance, CD4 T-cell counts, and disease progression in Danish individuals by polymerase chain reaction (PCR)-based methods as well as sequenced full-length CXCR4 and CCR5 genes from HIV-infected long-term nonprogressors for possible mutations. In total, 215 Danish individuals were analyzed for 64I allele frequency; disease progression was followed in 105 HIV-1-positive homosexual Danish men from their first known positive HIV-1 test result and up to 11 years. In 87 individuals, the CD4 T-cell count was monitored closely. We found no significant difference in 64I allele frequency between HIV-1-seropositive persons (0.08), high-risk HIV-1-seronegative persons (0.11), and blood donors (0.06). No significant difference was observed in annual CD4 T-cell decline, CD4 T-cell counts at the time of AIDS, in AIDS-free survival as well as survival with AIDS, between 64I allele carriers and wild-type individuals. Among 9 long-term nonprogressors, 2 carried the 64I allele, while none of 9 fast progressors carried the 64I allele. However, this was not significantly different (p=.47). Long-term nonprogression could not be explained by CXCR4 polymorphism or other polymorphisms in the CCR5 gene than the CCR5delta32 allele. Furthermore, we were not able to detect any significant independent effect of the 64I allele on development to AIDS, overall survival, and annual CD4 T-cell decline in this cohort.

摘要

我们通过基于聚合酶链反应(PCR)的方法,研究了最近描述的CCR2b基因中名为64I的突变在丹麦人群中与HIV耐药性、CD4 T细胞计数及疾病进展的关系,同时对HIV感染的长期非进展者的全长CXCR4和CCR5基因进行测序以寻找可能的突变。总共对215名丹麦人分析了64I等位基因频率;对105名HIV-1阳性的丹麦同性恋男性从首次已知HIV-1阳性检测结果开始随访长达11年,观察疾病进展情况。对87名个体密切监测CD4 T细胞计数。我们发现HIV-1血清阳性者(0.08)、高危HIV-1血清阴性者(0.11)和献血者(0.06)之间的64I等位基因频率无显著差异。64I等位基因携带者与野生型个体在每年CD4 T细胞下降、艾滋病时的CD4 T细胞计数、无艾滋病生存期以及患艾滋病后的生存期方面均未观察到显著差异。在9名长期非进展者中,2名携带64I等位基因,而9名快速进展者中无人携带64I等位基因。然而,这一差异无统计学意义(p = 0.47)。长期非进展不能用CXCR4多态性或CCR5基因中除CCR5delta32等位基因外的其他多态性来解释。此外,在该队列中,我们未能检测到64I等位基因对艾滋病发展、总体生存及每年CD4 T细胞下降有任何显著的独立影响。

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