Kaur Gurvinder, Singh P, Rapthap C C, Kumar N, Vajpayee M, Sharma S K, Wanchu A, Mehra N K
Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
Hum Immunol. 2007 May;68(5):454-61. doi: 10.1016/j.humimm.2007.01.016. Epub 2007 Feb 20.
The clinical course and outcome of human immunodeficiency virus-1 (HIV-1) infection are highly variable among individuals. CCR5 is the primary coreceptor that mediates entry of HIV-1 (R5) into permissive host cells. In this study, five SNPs (59029G/A, 59353T/C, 59356C/T, 59402A/G, and 59653C/T) in the promoter region and a deletion of 32 bp (Delta32) in the CCR5 gene were evaluated in 180 chronically HIV-1-infected North Indians. The study showed the following: (1) the protective CCR5 Delta32 allele was absent; (2) the frequency of CCR559402A allele in the HIV-infected people (66.4%) was higher than in healthy subjects (57.1%, p = 0.027) and in the CDC stage C patients (76%) versus stages A and B patients together (60%; p = 0.002); (3) homozygous CCR559402 AA genotype was significantly increased in the seropositive subjects (46.1%) compared with healthy control subjects (30.2%; p = 0.008) and in the CDC stage C patients (59.2%) compared with stage A and B subjects (37.6%, p = 0.007); and (4) an increased frequency of homozygous ACCAC haplotype was present in the seropositive stage C patients (32.4%) versus 15.6% in patients in stages A plus B (p = 0.013). These observations suggest an association of CCR5*59402A with increased likelihood of acquisition of HIV-1 and development of AIDS in the Asian Indian population. Further studies are required to confirm these findings and understand the effect of CCR5 polymorphisms on the outcome of HIV-1 infection.
人类免疫缺陷病毒1型(HIV-1)感染的临床病程和结果在个体之间差异很大。CCR5是介导HIV-1(R5)进入易感宿主细胞的主要共受体。在本研究中,对180名长期感染HIV-1的北印度人评估了CCR5基因启动子区域的5个单核苷酸多态性(59029G/A、59353T/C、59356C/T、59402A/G和59653C/T)以及一个32 bp的缺失(Delta32)。该研究显示如下结果:(1)保护性CCR5 Delta32等位基因不存在;(2)HIV感染者中CCR559402A等位基因的频率(66.4%)高于健康受试者(57.1%,p = 0.027),且在疾病控制与预防中心(CDC)C期患者中(76%)高于A期和B期患者合并组(60%;p = 0.002);(3)与健康对照受试者(30.2%;p = 0.008)相比,血清阳性受试者中纯合CCR559402 AA基因型显著增加,与A期和B期受试者(37.6%,p = 0.007)相比,CDC C期患者中该基因型也显著增加;(4)血清阳性C期患者中纯合ACCAC单倍型的频率增加(32.4%),而A期加B期患者中为15.6%(p = 0.013)。这些观察结果表明,在亚洲印度人群中,CCR5*59402A与感染HIV-1及发展为艾滋病的可能性增加有关。需要进一步研究来证实这些发现,并了解CCR5多态性对HIV-1感染结果的影响。