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。     

中国HIV-1感染者相关基因SDF1、CCR2b、CCR5多态性分析

目的分析91例中国HIV-1感染人群SDF1、CCR2b、CCR5等位基因型的多态性和分布特点。方法应用聚合酶链反应(PCR)、限制性片段长度多态性(RFLP)分析技术和核酸测序技术分析HIV-1感染人群SDF1、CCR2b、CCR5基因多态性。结果未发现91例中国HIV-1感染者有CCR5△32突变型基因,SDF1-3'A、CCR2b-64I等位基因突变频率分别为26.40%、2.43%,核酸测序结果与PCR/RFLP分析结果一致。结论91例中国HIV-1感染者均为易感者,中国HIV-1感染者SDF1、CCR2b、CCR5不同基因型分布特点,提示,中国人群可能对HIV-1有较大易感性。     

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。     

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。     

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.     

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.     

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。     

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     

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     

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     

中国蒙古族人群中人类免疫缺陷病毒1感染相关的基因多态性的初步研究

目的 调查中国蒙古族人群中与人类免疫缺陷病毒１（ＨＩＶ－１）感染相关的等位基因ＣＣＲ５－△３２、ＣＣＲ２ｂ－６４１和ＳＤＦ１－３′Ａ的频率和多态性分布。方法 随机采集血样,提取基因组ＤＮＡ,经聚合酶链式反应（ＰＣＲ）或聚合酶链式反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）电泳分析,计算各个突变基因的频率;并对其群体分布、性别分布和三者的相关性进行统计分析,同时与其他已报道的种族人群进行比较。结果     

The genetic variation of CCR5, CXCR4 and SDF-1 in three Chinese ethnic populations

The chemokine receptors and ligand CCR5, CXCR4 and SDF-1 play important roles in the entry of HIV-1 into host cells. Genetic polymorphisms such as CCR5-Δ32 and SDF-1 3'A have been reported to be associated with HIV-1 susceptibility and the progression of AIDS. Considering the remarkable difference in CCR5-Δ32 allele frequency among worldwide populations, we aimed to survey the genetic variations in CCR5, CXCR4 and SDF-1 in different Chinese populations. The open reading frames and regulatory regions of CCR5, CXCR4 and SDF-1 were sequenced in 141 Chinese individuals from three ethnic groups: Han, Mongol and Uyghur. Ninety-six variants were identified, 41 of which were newly identified (NI) in Chinese populations. A novel non-synonymous variant c.459 C>T (Trp153Cys) within CCR5 was identified in one Han individual. Of NI variants, 11 were common polymorphisms with a minor allele frequency (MAF) >5%. The polymorphism CCR5-Δ32 was found in three Uyghur individuals but was absent in Han and Mongol groups. The linkage disequilibrium (LD) analysis of CCR5 and SDF-1 and frequency of CCR5 haplotypes showed considerable divergence among three ethnic groups. Our results show the great genetic heterogeneity within CCR5, CXCR4 and SDF-1 in Chinese ethnic populations.     

Distribution of CCR5-Δ32, CCR5m303A,CCR2-64I and SDF1-3′A in HIV-1 infected and uninfected high-risk Uighurs in Xinjiang,China

BackgroundGenetic variants of the genes encoding HIV-1 co-receptors and their ligands, CCR5-Δ32, CCR5m303A, CCR2-64I and SDF1-3′A, are implicated in the susceptibility to HIV-1 infection, and the prevalence of these mutations varies by ethnicity. However, little is known about their distribution in Uighurs.ObjectivesThis study aimed at characterizing the frequency of these HIV-related gene variants in a high-risk Uighur population.Study designsA total of 251 HIV-1 seropositive and 238 seronegative high-risk Uighurs were recruited and their genotypes of CCR5-Δ32, CCR5m303A, CCR2-64I and SDF1-3′A were analyzed by PCR and PCR-ligase detection reaction (PCR-LDR).ResultsThe allelic frequency of CCR5-Δ32, CCR5m303A, CCR2-64I and SDF1-3′A was 4.40%, 2.66%, 25.66% and 57.36%, respectively, in this population. Apparently, the Uighur population has low frequency of CCR5-Δ32 and CCR5m303A, but high frequency of CCR2-64I and SDF1-3′A. While there was no significant difference in the frequency of CCR5-Δ32, CCR2-64I and SDF1-3′ A between HIV-1 seropositive and seronegative groups the frequency of CCR5m303A in HIV-1 seropositive group was significantly higher than that in seronegative group (P = 0.006, OR = 3.982 and 95%CI 1.514–10.476).ConclusionsOur data suggest that the CCR5-Δ32, CCR2-64I and SDF1-3′A variants may have limited effect on protecting from HIV-1 infection in Uighurs. Rather, the CCR5m303A may be associated with the risk for HIV-1 infection in high-risk Uighurs.     

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。     

HIV Infection and Host Genetic Mutation among Injecting Drug-users of Northeastern States of India

A community-based cross-sectional study was conducted among injecting drug-users (IDUs) of the northeastern states of India to understand the host genetic factors that confer resistance to HIV infection. The study aimed at assessing the existence and magnitude of genetic mutations of chemokine receptors, such as CCR2-64I, CCR-5 D-32, and SDF-1-3‘A, that are known to confer resistance to HIV infection and progression of disease in some set-ups. In total, 711 IDUs from Manipur, Mizoram, Nagaland, and Meghalaya were sampled for the study. The selected participants were interviewed to study their sociodemography, risk behaviours, and risk perceptions after obtaining their verbal informed consent. The interview was followed by collection of about 5 mL of blood samples by an unlinked anonymous method for studying genetic mutation and HIV infection. All the blood samples were transported to and processed at the clinical medicine laboratory of the National Institute of Cholera & Enteric Diseases, Kolkata, India. The genetic mutations were detected by polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) assay techniques. The study revealed that 328 (46.1%) IDUs were aged 20–29 years, 305 (42.9%) were aged 30–39 years, and only two (0.3%) were aged above 49 years. The rate of HIV seropositivity varied widely among the IDUs living in different northeastern states that ranged from 4.5% to 61%. There was not a single IDU with CCR5 homozygous mutation. Mutated genes of CCR2-64I and SDF-1-3''A were detected in the frequencies of 49% and 23% respectively in them. The rate of HIV seropositivity in IDUs having CCR2 mutant gene was 27% (n=94) and without mutation was 27% (n=98). Similarly, HIV seropositivity in IDUs with and without SDF1 mutation was 28% (n=46) and 27% (n=146) respectively. Both the differences were not statistically significant. A CCR5 homozygous mutation is known to be the most prominent marker that confers resistance against HIV infection. The absence of CCR5 mutant gene in this population suggests that they do not have any additional protection against HIV infection. Analysis also revealed that, although mutation of CCR2 and SDF1 was present in this population, it did not confer any additional resistance against HIV. This indicates that the IDUs of northeastern India are not additionally protected against HIV infection through genetic mutation and are, therefore, vulnerable to acquire HIV infection due to high-risk behaviour and other related factors.Key words: Community-based studies, Cross-sectional studies, Genetic mutation, HIV infections, Sexually transmitted diseases, Substrance-use, India