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首页> 外文期刊>International journal of immunogenetics >Polymorphism in the proximal promoter region of the perforin gene and its impact on the course of HIV infection.
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Polymorphism in the proximal promoter region of the perforin gene and its impact on the course of HIV infection.

机译：穿孔素基因近端启动子区域的多态性及其对HIV感染过程的影响。

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摘要

Cytotoxic T lymphocytes (CTLs) play an essential role in the control of viral replication during human immunodeficiency virus (HIV) infection. However, the efficacy of the CTL response varies between individuals. We tested the hypothesis that genetic polymorphisms in the lytic effector molecule perforin could influence the progression of HIV infection. The perforin gene was screened for single nucleotide polymorphisms (SNPs) by denaturing high-performance liquid chromatography (dHPLC). Correlations were sought between perforin genotype, perforin expression and lytic function of CD8+ T lymphocytes from HIV-positive patients. Association of perforin genotype with disease progression was investigated in 426 seroconverters enrolled in the French SEROCO cohort. AIDS-free survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Three SNPs were found in the proximal promoter region of the perforin gene: 63G (allelic frequency 0.029), 112G (allelic frequency 0.071) and 1012T (allelic frequency 0.070). The presence of the 1012T genotype correlated with fewer perforin+ cells among circulating CD8+ CTL. However, CTL lines from HIV(-positive) individuals heterozygous for the perforin 1012T SNP displayed normal lysis of target cells, and within the SEROCO cohort, patients heterozygous for the 1012T SNP showed normal disease progression. However, 1012T/T homozygotes showed a tendency towards slower disease progression (P = 0.08). In conclusion, polymorphism in the perforin gene is limited, and although the 1012T genotype appears to influence perforin expression, it was not conclusively associated with disease progression in HIV infection.
机译：细胞毒性T淋巴细胞（CTL）在人类免疫缺陷病毒（HIV）感染过程中的病毒复制控制中起着至关重要的作用。但是，CTL反应的功效因人而异。我们检验了以下假设，即裂解效应分子穿孔素中的遗传多态性可能影响HIV感染的进程。通过变性高效液相色谱（dHPLC）筛选穿孔素基因的单核苷酸多态性（SNP）。寻求HIV阳性患者的穿孔素基因型，穿孔素表达与CD8 + T淋巴细胞溶解功能之间的相关性。在法国SEROCO队列的426名血清转化者中研究了穿孔素基因型与疾病进展的关系。使用Kaplan-Meier方法构建无艾滋病生存曲线，并使用对数秩检验进行比较。在穿孔素基因的近端启动子区域中发现了三个SNP：63G（等位基因频率0.029），112G（等位基因频率0.071）和1012T（等位基因频率0.070）。 1012T基因型的存在与循环CD8 + CTL中较少的穿孔素+细胞相关。但是，来自穿孔穿孔1012T SNP杂合子的HIV（阳性）个体的CTL系显示靶细胞正常裂解，在SEROCO队列中，1012T SNP杂合子的患者显示正常疾病进展。然而，1012T / T纯合子显示出疾病进展较慢的趋势（P = 0.08）。总之，穿孔素基因的多态性是有限的，尽管1012T基因型似乎影响穿孔素的表达，但它与HIV感染的疾病进展并没有结论性的联系。

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