Verma Romsha, Gupta Radha Ballabh, Singh Kalpana, Bhasin Rama, Anand Shukla Abhay, Chauhan Shyam S, Luthra Kalpana
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
J Clin Virol. 2007 Mar;38(3):198-203. doi: 10.1016/j.jcv.2006.12.006. Epub 2007 Jan 19.
Host genetic factors play an important role in susceptibility to HIV-1 infection and progression to AIDS. Mutations in genes encoding chemokine receptors and their ligands, viz., CCR5delta32, CCR2-64I and SDF1-3'A are implicated to have protective effects against HIV-1 infection and/or disease progression. The distribution of these gene polymorphisms and their role in the course of the disease varies between individuals of different racial, ethnic and risk groups. We have examined the allelic frequencies of CCR5delta32, CCR2-64I and SDF1-3'A in 500 healthy North Indians tested seronegative for HIV-1, by PCR-RFLP. The plasma levels of stromal derived factor (SDF-1) protein were estimated in 75 individuals using ELISA kit. Frequencies of CCR5delta32, CCR2-64I and SDF1-3'A alleles in 500 individuals were 1.5%, 9.1% and 20.4%, respectively. The SDF1-3'A homozygosity was confirmed by PCR product cloning and sequencing. The relative hazard values calculated on the basis of the three locus genotype of each individual revealed high relative hazard values (>0.9). The plasma levels of SDF-1 ranged from 1.77 to 3.42 ng/ml and were comparable between the three genotypes of SDF-1. This is the first study to assess the plasma level of SDF-1 protein in Asian Indians. Low frequency of the protective allele CCR5delta32 observed in this study suggests high vulnerability of North Indians to HIV-1 infection. The precise role of SDF1-3'A in HIV-1 infection needs to be elucidated.
宿主遗传因素在HIV-1感染易感性及发展为艾滋病的过程中起重要作用。编码趋化因子受体及其配体的基因发生突变,即CCR5delta32、CCR2-64I和SDF1-3'A,被认为对HIV-1感染和/或疾病进展具有保护作用。这些基因多态性的分布及其在疾病过程中的作用在不同种族、民族和风险群体的个体之间存在差异。我们通过PCR-RFLP检测了500名HIV-1血清学阴性的健康北印度人的CCR5delta32、CCR2-64I和SDF1-3'A的等位基因频率。使用ELISA试剂盒对75名个体的基质衍生因子(SDF-1)蛋白的血浆水平进行了评估。500名个体中CCR5delta32、CCR2-64I和SDF1-3'A等位基因的频率分别为1.5%、9.1%和20.4%。通过PCR产物克隆和测序证实了SDF1-3'A纯合性。根据每个个体的三个基因座基因型计算的相对风险值显示出较高的相对风险值(>0.9)。SDF-1的血浆水平在1.77至3.42 ng/ml之间,在SDF-1的三种基因型之间具有可比性。这是第一项评估亚洲印度人血浆中SDF-1蛋白水平的研究。本研究中观察到的保护性等位基因CCR5delta32的低频率表明北印度人对HIV-1感染具有高度易感性。SDF1-3'A在HIV-1感染中的精确作用需要阐明。