应用RFLP技术分析HIV感染相关基因的多态性

目的：评估不同人群对HIV的遗传易感性，为制定艾滋病的预防和控制策略提供科学依据。方法：应用PCR／RFLP技术进行HIV感染相关基因SDF1、CCR2b、CCR5的多态性分析，并用核酸测序技术进行验证。结果：发现PCR／RFLP分析结果与核酸测序结果一致，该方法便于操作、成本较低。结论：可以将PCR／RFLP分析方法应用于HIV感染相关基因多态性的人群分布调查，为今后深入研究中国人SDF1、CCR2b、CCR5各基因型的分布频率打下基础。     

人类免疫缺陷病毒1感染相关的基因多态性在中国汉族人群中的分布

目的　调查中国汉族人群中人类免疫缺陷病毒 1(HIV 1)感染相关的CCR5△ 32、CCR2 6 4I和SDF1 3’A等位基因突变频率和多态性的特点。方法　以 12 5 1例汉族人群为研究对象 ,应用PCR、PCR/RFLP(聚合酶链反应 /限制性片段长度多态性分析 )和DNA直接测序等方法进行检测 ,并用统计学方法进行分析。结果　发现中国汉族人群中存在CCR5△ 32等位基因突变 (均为杂合子基因型 ) ,突变频率为 0 .0 0 119,和西欧及美国白人相比 ,中国人群中CCR5△ 32基因突变频率极低 ,而CCR2 6 4I和SDF1 3’A基因突变频率相对较高 ,分别为 0 .2 0 0 2 3和 0 .2 872 3。结论　中国汉族人群的CCR5△ 32、CCR2 6 4I和SDF1 3’A等位基因的突变和多态性特点 ,具有一定的代表性。由于CCR5△ 32突变率低 ,中国汉族人群对性接触传播的HIV 1病毒 (R5 )株可能有较大的遗传易感性     

HIV-1感染相关基因突变频率及多态性研究

目的 研究山东省济南市人群中与人类免疫缺陷病毒(HIV)-1感染相关的CCR2～64I和SDF1-3′A等位基因的突变频率和多态性特点。方法 以234例济南市普通人群为研究对象，来自商河和章丘2个县，其中无1例是HIV感染者，从上述人群外周血的外周血单干核细胞(PBMC)中抽提基因组DNA，然后应用PCR／限制性片断长度多态性(RFLP)检测去化因子受体(CCR)2．64I和基质细胞衍生因子(SDF)1．3多态性。结果 济南市人群中存在CCR2．64I和SDF1-3′A等位基因突变，2种突变频率分别为20．25％和21．00％，两等位基因型的分布均符合HardyWeinberg平衡。结论 济南市人群CCR2．64I和SDF1-3′A等位基因的突变频率较高，人群对HIV-1感染的遗传易感性相对较低。     

四川彝族人群HIV-1辅助受体CCR5△32和CCR2-64I基因多态性分析

目的了解中国四川彝族人群艾滋病病毒-1(HIV-1)辅助受体CCR5△32和CCR2．64I基因多态性特点。方法提取119份彝族正常人和88份HIV-1感染人群外周血基因组DNA。用聚合酶链反应(PCR)方法检测CCR5△32突变,阳性产物经克隆、测序进一步证实;用PCR-限制性片段长度多态性技术检测CCR2．64I突变,并测序验证。结果119份正常人样本中,CCR5 wt／△32等位基因突变杂合子2例(1．68％),未检测到CCR5△32／△32突变纯合子,CCR5△32等位基因频率为0．0084;CCR2-64I突变杂合子26例(21．85％),突变纯合子2例(1．68％),等位基因频率为01261。88份HIV-1感染者样本中,未检测到CCR5△32突变;CCR2．64I突变杂合子12例(13．64％),突变纯合子7例(7．95％),等位基因频率为0．1327。统计分析表明,上述等位基因多态性在该群体中均呈Hardy-Weinberg平衡分布;两种等位基因的突变频率在正常人和感染人群中的差异均无统计学意义。结论研究获得了中国四川彝族人群CCR5△32、CCR2-64I等位基因多态性资料,结果有助于综合评估中国人群对HIV-1感染的遗传易感性,同时为深入研究HIV-1抗性基因在中国不同民族的HIV感染及发病机制中的作用奠定基础。     

广西壮、汉族人群HIV-1感染相关基因CCR2-64I和SDF1-3'A多态性的研究

[目的]研究HIV-1感染相关的CCR2-64I及SDF1-3'A等位基因在广西壮、汉族人群的突变频率和多态性特点. [方法]抽取广西天等县、南宁市100名壮族和50名汉族人,提取全血基因组DNA,采用PCR-限制性片段长度多态性(PCR-RFLP)方法检测CCR2-64I和SDF1-3'A的基因多态性,分析CCR2-64I及SDF1-3'A等位基因在研究人群中的分布及其特征.[结果]壮族、汉族人群中CCR2-64I等位基因突变频率分别为25.5%、26.0%,SDF1-3'A等位基因突变频率均为27.0%,CCR2-64I和SDF1-3'A等位基因突变频率在壮、汉族之间差异无统计学意义(P>0.1).[结论]广西壮、汉族人群中具有较高的CCR2-64I及SDF1-3'A等位基因.本研究了解广西壮、汉族人群中CCR2-64I和SDF1-3'A等位基因的分布和多态性特点,为进一步深入研究广西壮、汉族人群的遗传背景与HIV感染及疾病病程的关系提供了重要数据.     

云南省景颇族人群HIV-1感染相关基因多态性研究

目的:了解云南省景颇族人群与HIV-1感染相关基因CCR5-Δ32、CCR2-64I、SDF1-3′A的频率和多态性分布。方法:以云南省113例景颇族人群为研究对象,采用PCR、PCB/RFLP(聚合酶链式反应/限制性片段长度多态性分析)计算基因频率,并用统计学方法进行分析。结果:未发现CCR5-Δ32突变;CCR2-64I突变基因频率为16.37％;SDF1-3′G/3′G突变基因频率为17.70％,突变基因频率低于汉族。结论:由于未发现CCR5-Δ32突变和SDF1-3′G/3′G等位基因频率较低,云南省景颇族人群可能比汉族人对HIV-1(包括R5和X4HIV-1)有较大的遗传易感性。     

亚洲人群中SDF1-3’A和CCR2-64I基因的多态性与HIV-1感染相关性的Meta分析

目的探讨SDF1-3’A和CCR2-64I基因的多态性与HIV-1感染之间的关联性。方法检索国内外有关SDF1-3’A和CCR2-64I基因的多态性与HIV感染相关性的病例对照研究文献进行Meta分析。结果符合CCR2-64I入选条件的文献有13篇,20个研究,总共有5 578例样本,其中病例有2 898例,健康对照有2 680例,当CCR2-64I基因所入选的研究全部合并在一起时,在所有模型中没有发现其显著相关性(CY vs.CC:OR=0.97,95%CI=0.85~1.09;CY+YY vs.YY:OR=1.00,95%CI=0.89~1.13;YY vs.CC:OR=1.28,95%CI=0.97~1.69)。符合SDF1-3’A入选条件的文献13篇,19个研究,总共有4 854例,其中病例有2 281例,健康对照有2 573例,在整个和亚组分析中没有发现其显著相关性。而在印度人群发现高度的异质性。结论亚洲人群CCR2-64I两种抗性基因与HIV-1感染之间无相关性;中国人群SDF1-3’A与HIV-1感染之间无相关性;印度人群SDF1-3’A与HIV-1感染之间是否有相关性仍需作进一步的研究。     

亚洲人群中SDF1-3’A和CCR2-64I基因的多态性与HIV-1感染相关性的Meta分析

目的探讨SDF1-3’A和CCR2-64I基因的多态性与HIV-1感染之间的关联性。方法检索国内外有关SDF1-3’A和CCR2-64I基因的多态性与HIV感染相关性的病例对照研究文献进行Meta分析。结果符合CCR2-64I入选条件的文献有13篇,20个研究,总共有5578例样本,其中病例有2898例,健康对照有2680例,当CCR2-64I基因所入选的研究全部合并在一起时,在所有模型中没有发现其显著相关性（CY vs. CC: OR = 0.97,95% CI = 0.85-1.09; CY + YY vs. YY: OR = 1.00,95% CI = 0.89-1.13;YY vs. CC：OR = 1.28,95% CI = 0.97-1.69）。符合SDF1-3’A入选条件的文献13篇,19个研究,总共有4854例,其中病例有2281例,健康对照有2573例,在整个和亚组分析中没有发现其显著相关性。而在印度人群发现高度的异质性。结论亚洲人群CCR2-64I两种抗性基因与HIV-1感染之间无相关性;中国人群SDF1-3’A与HIV-1感染之间无相关性;印度人群SDF1-3’A与HIV-1感染之间是否有相关性仍需作进一步的研究。     

HIV-1感染相关基因的多态性研究进展

近年来,通过对人免疫缺陷病毒I型(HIV-1)协同受体(如CCR5、CXCR4、CCR2、CCR3和CXCR4的天然配基SDF1等)的基因多态性分析,发现CCR5-△32等位基因型的个体对M-tropic病毒株感染有天然的抵抗力;CCR5-△32和CCR2-64I等位基因型分别对艾滋病(AIDS)的发病进程有显著的延缓作用,SDF1-3′A等位基因型也直接影响到AIDS的预后。因此,协同受体的发现使HIV-1感染和AIDS发病机制的研究有了重大的突破。尤其是通过揭示CCR5、CCR2和SDF1等基因多态性与HIV-1感染的相互关系及特点,对AIDS的预防、诊断和治疗都具有重要的意义。     

HIV-1辅助受体及配体基因多态性在新疆高危人群中的分布

CD4分子和一些辅助受体是HIV-1识别、黏附并入侵宿主细胞所必需的.CCR5和CXCR4是HIV-1最主要的2个辅助受体,此外一些HIV还可利用CCR2等作为辅助受体.研究发现,这些辅助受体及其配体的某些基因多态性与HIV-1易感和/或疾病进展相关[1].影响HIV-1易感性及AIDS进展的基因多态性在维吾尔族的分布尚不明确.本研究采用PCR和PCR-连接酶检测反应(PCR-LDR)技术检测CCR5A32、CCR5m303A、CCR2-64I、SDF1-3'A和RANTES inl.1T/C基因多态性在维吾尔族人群中的分布.     

人类免疫缺陷病毒1感染相关的基因多态性在中国汉族人群中的分布

目的：调查中国汉族人群中人类免疫缺陷病毒１（ＨＩＶ－１）感染相关的ＣＣＲ５Δ３２、ＣＣＲ２－６４１和ＳＤＦ１－３‘Ａ等位基因突变频率和多态性的特点。方法：以１２５１例汉族人群为研究对象,应用ＰＣＲ、ＰＣＲ／ＲＦＬＰ（聚合酶链反应／限制性片段长度多态性分析）和ＤＮＡ直接测序等方法进行检测,并用统计学方法进行分析。结果：发现中国汉族人群中存在ＣＣＲ５Δ３２等位基因突变（均为杂合子基因型）,突变频率为１     

CCR2, CCR5, and CXCL12 variation and HIV/AIDS in Papua New Guinea

Polymorphisms in chemokine receptors, serving as HIV co-receptors, and their ligands are among the well-known host genetic factors associated with susceptibility to HIV infection and/or disease progression. Papua New Guinea (PNG) has one of the highest adult HIV prevalences in the Asia-Pacific region. However, information regarding the distribution of polymorphisms in chemokine receptor (CCR5, CCR2) and chemokine (CXCL12) genes in PNG is very limited. In this study, we genotyped a total of nine CCR2-CCR5 polymorphisms, including CCR2 190G > A, CCR5 − 2459G > A and Δ32, and CXCL12 801G > A in PNG (n = 258), North America (n = 184), and five countries in West Africa (n = 178). Using this data, we determined previously characterized CCR5 haplotypes. In addition, based on the previously reported associations of CCR2 190, CCR5 − 2459, CCR5 open reading frame, and CXCL12 801 genotypes with HIV acquisition and/or disease progression, we calculated composite full risk scores, considering both protective as well as susceptibility effects of the CXCL12 801 AA genotype. We observed a very high frequency of the CCR5 − 2459A allele (0.98) in the PNG population, which together with the absence of Δ32 resulted in a very high frequency of the HHE haplotype (0.92). These frequencies were significantly higher than in any other population (all P-values < 0.001). Regardless of whether we considered the CXCL12 801 AA genotype protective or susceptible, the risk scores were significantly higher in the PNG population compared with any other population (all P-values < 0.001). The results of this study provide new insights regarding CCR5 variation in the PNG population, and suggest that the collective variation in CCR2, CCR5, and CXCL12 may increase the risk of HIV/AIDS in a large majority of Papua New Guineans.     

基质衍生因子1等基因多态性在人群中的分布

目的　探讨SDF1-3’A、CCR2 -64I、-2 518MCP -1基因多态性在皖籍汉族人群中的分布。方法　运用PCR -RFLP方法确定SDF1-3 /A和 -2 518MCP -1基因多态性 ,运用ARMS方法确定CCR2 -64I基因多态性。结果　皖籍汉族人 -2 518MCP -1G等位基因突变频率为 64% ,高于西班牙人、美国黑人、高加索人 ,均有显著性差异(P <0 0 1)。CCR2 -64I等位基因突变频率为 2 5% ,高于美国黑人和高加索人 (P <0 0 1)。SDF1-3’A等位基因突变频率为 2 2 % ,高于美国黑人 ,但与国内其他地区均无显著性差异 (P <0 0 5)。结论　皖籍汉族人 -2 518MCP -1、CCR2 -64I、SDF1-3’A等位基因突变频率有别于其他人种     

Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection

Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host’s susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES −403A/G, RANTES −28C/G and SDF1 3′-A) were screened. CCR5Δ32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts’ genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3′-A were not associated with host’s resistance to HIV-1 infection. The frequency of RANTES −403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p = 0.0005) and HESN group (p = 0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG + AG, OR = 0.38 95% CI, 0.22–0.65 p = 0.0004; A vs. G, OR = 0.66 95% CI, 0.52–0.84 p = 0.0006), which supported this association, either. The genotype and allele distribution of RANTES −28 between HIV-1 patients and healthy controls (genotype profile: p = 0.072; allele profile: p = 0.027) or HIV-1 seronegative group (genotype profile: p = 0.036; allele profile: p = 0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES −403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES −28 locus not. By lack of the patients’ clinical information, whether these polymorphisms affect AIDS disease progression and their role in different HIV-1 infection routes could not performed in present study and needs to be assessed in ongoing studies.     

CCR5受体拮抗剂治疗艾滋病的研究进展

UK-427,857(maraviroc)是一个选择性CCR5受体拮抗剂,有很强的对抗HIV-1活性,是药理学的一个重大骄人成就。用化学素放射配体黏附实验的方法,从药物大典将近1000多种合成的类似物中筛选出来的UK-427,857,无论是从与受体的黏附力、抗病毒活性、吸收、药代动力学,还是人体内目标靶位的选择性来讲,都有着无可比拟的优点,因此它将成为治疗艾滋病最有潜力的药物。     

淋巴细胞表面CCR5在HCV与HIV感染中表达

目的探讨T淋巴细胞表面C—C趋化因子受体5（CCR5）在丙型肝炎病毒（HCV）感染、人类免疫缺陷病毒（HIV）感染和HCV／HIV合并感染过程中的表达及意义。方法采用流式细胞术检测HCV感染组（n=21例），HIV感染组（n=14例），HCV／HIV感染组（n=28例）及正常对照组（n=30例）人外周血CD4＋和CD8＋T淋巴细胞表面CCR5的表达。结果与正常对照组相比，外周血CD4^＋和CD8^＋T淋巴细胞表面CCR5，HIV感染组高表达（P〈0．01），HCV感染组和HCV／HIV合并感染组中低表达（P〈0．01）。结论淋巴细胞表面CCR5的表达，HIV感染时升高、HCV感染时降低，HCV／HIV合并感染时HCV感染的作用更强。     

HIV surveillance--United States, 1981-2008

Within 1 year of the initial report in 1981 of a deadly new disease that occurred predominantly in previously healthy persons and was manifested by Pneumocystis carinii pneumonia and Kaposi's sarcoma, the disease had a name: acquired immune deficiency syndrome (AIDS). Within 2 years, the causative agent had been identified: human immunodeficiency virus (HIV). On the 30th anniversary of the epidemic, to characterize trends in HIV infection and AIDS in the United States during 1981-2008, CDC analyzed data from the National HIV Surveillance System. This report summarizes the results of that analysis, which indicated that, in the first 14 years, sharp increases were reported in the number of new AIDS diagnoses and deaths among persons aged≥13 years, reaching highs of 75,457 in 1992 and 50,628 in 1995, respectively. With introduction of highly active antiretroviral therapy, AIDS diagnoses and deaths declined substantially from 1995 to 1998 and remained stable from 1999 to 2008 at an average of 38,279 AIDS diagnoses and 17,489 deaths per year, respectively. Despite the decline in AIDS cases and deaths, at the end of 2008 an estimated 1,178,350 persons were living with HIV, including 236,400 (20.1%) whose infection was undiagnosed. These findings underscore the importance of the National HIV/AIDS Strategy focus on reducing HIV risk behaviors, increasing opportunities for routine testing, and enhancing use of care (1).