Polymorphic variants in DC-SIGN, DC-SIGNR and SDF-1 in high risk seronegative and HIV-1 patients in Northern Asian Indians

Polymorphic variants in DC-SIGN, DC-SIGNR and SDF-1 in high risk seronegative and HIV-1 patients in Northern Asian Indians
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DOI:
10.1016/j.jcv.2008.06.005
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发表时间:
2008-10-01
影响因子:
8.8
通讯作者:
Luthra, Kalpana
Luthra, Kalpana
中科院分区:
医学3区
文献类型:
--
作者:
Chaudhary, Omkar;Rajsekar, Kavitha;Luthra, Kalpana

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SDF-1(HIV-1 辅助受体 CXCR4 的天然配体)中的单核苷酸多态性 (SNP) 具有针对 HIV-1 感染的保护作用。树突状细胞最先在粘膜部位遇到 HIV-1,病毒结合通过称为 DC-SIGN 的受体发生。据报道,DC-SIGN 和 DC-SIGNR 颈部区域重复次数的变化可能会影响宿主对 HIV-1 感染的易感性。我们通过 PCR 限制性片段长度多态性 (RFLP) 检查了 SDF1-3'A 的 SNP,并通过 PCR 检查了来自印度北部的健康 HIV 血清阴性个体、HIV 血清阴性高危 STD 患者和 HIV-1 血清阳性患者中 DC-SIGN 和 DC SIGNR 的重复区域多态性。通过克隆和测序证实了检测到的多态性。 100名HIV血清阴性健康个体、150名HIV血清阴性STD患者和100名HIV-1血清阳性患者中SDF1-3'A/SDF1-3'A的基因型频率分别为4%、18%和7%。与 HIV 血清阳性 (p = 0.014) 和健康的 HIV-1 血清阴性测试个体 (p = 0.001) 相比,在高风险 STD 患者中观察到 SDF1-3'A/SDF1-3'A 的频率显着更高,表明 SDF1-3'A 在 HIV-1 感染中具有保护作用。 DC-SIGN 多态性很少见,并且基因型 7/7 在所有研究组中占主导地位。 DC-SIGNR 具有高度多态性,在不同研究组中观察到 11 种基因型。 DC-SIGNR 多态性变体在人群中的确切作用需要阐明。 (C) 2008 年由 Elsevier B.V. 出版
A single nucleotide polymorphism (SNP) in SDF-1, the natural ligand for the HIV-1 coreceptor CXCR4, is implicated to have protective effects against HIV-1 infection. Dendritic cells are the first to encounter HIV-1 at mucosal sites and virus binding occurs via receptors known as DC-SIGN. Variations in the number of repeats in the neck region of DC-SIGN and DC-SIGNR are reported to possibly influence host susceptibility to HIV-1 infection. We examined the SNP of SDF1-3'A by PCR-restriction fragment length polymorphism (RFLP) and repeat region polymorphisms in DC-SIGN and DC SIGNR by PCR in healthy HIV seronegative individuals, high risk STD patients seronegative for HIV, and HIV-1 seropositive patients from northern India. The detected polymorphisms were confirmed by cloning and sequencing. The genotypic frequency of SDF1-3'A/SDF1-3'A in the 100 HIV-seronegative healthy individuals, 150 HIV seronegative STD patients, and 100 HIV-1 seropositive patients were 4%, 18% and 7%, respectively. A significantly higher frequency of SDF1-3'A/SDF1-3'A was observed in high risk STD patients as compared to HIV seropositive (p = 0.014) and healthy HIV-1 seronegative tested individuals (p = 0.001), suggesting a protective role of SDF1-3'A in HIV-1 infection. DC-SIGN polymorphism was rare and genotype 7/7 was predominant in all groups studied. DC-SIGNR was highly polymorphic and 11 genotypes were observed among the different study groups. The precise role of the polymorphic variants of DC-SIGNR needs to be elucidated in the population. (C) 2008 Published by Elsevier B.V.