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细胞限制基因(TRIM5α、BST-2)多态性对 HIV-1 获得和疾病进展的影响。

Impact of cellular restriction gene (TRIM5α, BST-2) polymorphisms on the acquisition of HIV-1 and disease progression.

机构信息

Department of Molecular Biology, National AIDS Research Institute, Pune, India.

Department of Clinical Sciences, National AIDS Research Institute, Pune, India.

出版信息

J Gene Med. 2018 Feb;20(2-3):e3004. doi: 10.1002/jgm.3004. Epub 2018 Jan 25.

DOI:10.1002/jgm.3004
PMID:29282802
Abstract

BACKGROUND

TRIM5α and BST-2 are cellular restriction factors affecting the HIV-1 infection and its progression. Genetic variability in these genes alters the expression pattern. Hence, we aimed to examine the impact of the TRIM5α (rs10838525, rs7127617 and rs904375) and BST2 (rs3217318 and rs71694748) polymorphisms on the acquisition of HIV-1 and its progression.

METHODS

Genotyping of TRIM5α and BST-2 polymorphisms was performed in a total of 153 HIV-infected patients and 158 unrelated healthy individuals using a polymerase chain reaction-restriction fragment length polymorphism method.

RESULTS

No significant differences were found in the genotype frequencies of TRIM5α polymorphisms between HIV patients and healthy controls. BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes appeared more frequently in HIV patients compared to healthy controls (10.4% versus 7.0%, p = 0.20; 11.10% versus 7.6%, p = 0.16). The BST-2 i19 allele was associated with the acquisition of HIV-1 [odds ratio (OR) = 2.76, p = 0.030)]. TRIM5α haplotypes ATG and ACA elevated the risk, whereas haplotype ATA reduced the risk for the acquisition of HIV-1 (OR = 1.92, p = 0.026; OR = 4.88, p = 0.016; OR = 0.31, p = 0.014). BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes were more prevalent in patients with early HIV disease stage compared to healthy controls (15.9% versus 7.0%, p = 0.096; 15.9% versus 7.6%, p = 0.12). The prevalence of TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes was observed to be higher in alcohol-using HIV patients compared to non-users (27.8% versus 20.0%, p = 0.35, 22.2% versus 10.0%, p = 0.24).

CONCLUSIONS

TRIM5α haplotypes and the BST-2 i19 allele may significantly affect the modulation of HIV-1 acquisition and its progression. TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes in alcohol-using HIV patients elevated the risk of HIV disease progression.

摘要

背景

TRIM5α 和 BST-2 是影响 HIV-1 感染及其进展的细胞限制因子。这些基因的遗传变异改变了表达模式。因此,我们旨在研究 TRIM5α(rs10838525、rs7127617 和 rs904375)和 BST2(rs3217318 和 rs71694748)多态性对 HIV-1 获得及其进展的影响。

方法

采用聚合酶链反应-限制性片段长度多态性方法,对 153 例 HIV 感染患者和 158 例无关健康个体的 TRIM5α 和 BST-2 多态性进行基因分型。

结果

HIV 患者与健康对照组之间 TRIM5α 多态性的基因型频率无显著差异。与健康对照组相比,BST-2 Δ19/i19 和 i19/i19+ Δ19/i19 基因型在 HIV 患者中更为常见(10.4%比 7.0%,p=0.20;11.10%比 7.6%,p=0.16)。BST-2 i19 等位基因与 HIV-1 的获得相关(比值比[OR] = 2.76,p = 0.030)。TRIM5α 单倍型 ATG 和 ACA 增加了风险,而单倍型 ATA 降低了 HIV-1 获得的风险(OR = 1.92,p = 0.026;OR = 4.88,p = 0.016;OR = 0.31,p = 0.014)。与健康对照组相比,早期 HIV 病期患者中 BST-2 Δ19/i19 和 i19/i19+ Δ19/i19 基因型更为常见(15.9%比 7.0%,p=0.096;15.9%比 7.6%,p=0.12)。与非饮酒者相比,HIV 患者中 TRIM5α rs7127617 CC 和 BST-2 Δ19/i19 基因型的频率更高(27.8%比 20.0%,p=0.35;22.2%比 10.0%,p=0.24)。

结论

TRIM5α 单倍型和 BST-2 i19 等位基因可能显著影响 HIV-1 获得及其进展的调节。HIV 患者中 TRIM5α rs7127617 CC 和 BST-2 Δ19/i19 基因型的使用增加了 HIV 疾病进展的风险。

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