西藏藏族人群白细胞介素1受体拮抗剂基因多态性

目的:研究白细胞介素-1受体拮抗剂(IL-1Ra)在西藏藏族健康人群中的分布特点,并与其他不同人群进行比较.方法:采用PCR的方法,对125名西藏拉萨市藏族人群IL-1Ra基因的可变数目串联重复序列多态性进行检测,计算其基因型频率和等位基因频率,并结合文献与其他不同人群进行比较分析.结果:西藏藏族人群IL-1Ra位点基因型以A1/A1纯合子型最为多见(频率为90.40%),A1/A2杂合子型次之(频率为9.60%),A2/A2纯合子型未检测到;其等位基因分布也是以A1等位基因最为多见 (频率为95.20%),其次为A2等位基因(频率为4.80%).西藏藏族人群的等位基因频率分布与美国人、德国人、非洲白人差异较大,具有统计学意义.而与亚洲人群包括日本人和中国汉族差异较小.结论:西藏拉萨市藏族人群中IL-1Ra位点以A1等位基因为主,其多态性分布与其他人群之间存在明显的差异,为进一步研究IL-1Ra基因多态性与疾病的关系奠定了基础.     

云南傣族景颇族人群中与艾滋病相关的CX3CR1基因多态性分布

目的调查HIV-1感染相关的等位基因CX3CR1的单核苷酸多态在我国云南省德宏州傣族、景颇族人群中的分布.方法以101例傣族人群和113例景颇族人群为研究对象,应用聚合酶链式反应-限制性片段长度多态(PCR-RFLP)分析方法,研究CX3CR1基因序列中249和280位点碱基是否发生突变,并对其群体分布、性别分布进行统计学分析.结果中国傣族人群中I249和M280突变基因频率分别为0.0495和0.0297;中国景颇族人群中I249和M280突变基因频率分别为0.0530和0.0221.结论中国云南傣族、景颇族人群存在CX3CR1基因序列中249和280位点突变,突变频率与国内外各种族相比具有一定的可比性.本实验为国内首次对我国傣族、景颇族人群的HIV-1感染协同受体基因CX3CR1进行收集和分析,这在傣族、景颇族人群艾滋病的预防和治疗方面的意义值得深入研究.     

广东地区汉族人群的hGSTP1Ile105Val基因多态性的研究

目的:对广东地区汉族人群的hGSTP1Ile105Val基因多态性进行研究。方法:应用PCR-RFLP(基因体外扩增限制性片段长度多态性分析)的技术方法进行研究。结果:该人群中GSTP1基因在105位点的野生型纯合子(AA)基因型的分布频率为57.4%,突变型纯合子(GG)基因型为6.7%,杂合子(AG)基因型为35.9%。结论:GSTP1纯合突变基因型在广东地区汉族人群中的分布频率为6.7%。     

西藏藏族人群白细胞介素1β基因+3953 C/T多态性

目的:研究白细胞介素1β(IL-1β)第5外显子+3953位点核苷酸C/T多态性(SNP)在西藏藏族健康人群中的分布特点,并与其他不同种族进行比较.方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法,对125名西藏拉萨市藏族人群IL-1β +3953位点SNP进行检测,计算其基因型频率和等位基因频率,并结合文献与其他不同种族进行比较分析.结果:西藏拉萨市藏族人群IL-1β +3953位点基因型以CC 纯合子型最为多见,(频率为91.20%),CT杂合子型次之(8.00%),TT纯合子型很少(0.80%);其等位基因分布也是以C等位基因最为多见(95.20%),其次为T等位基因(4.80%).西藏藏族人群的等位基因频率分布与德国、西班牙人、高加索人的差异较大,具有统计学意义.而与亚洲人群包括日本人和湖北汉族、广西汉族、广西壮族差异无统计学意义.结论:西藏拉萨市藏族人群中IL-1β +3953位点以C等位基因为主,其SNP分布与其他种族之间存在差异.     

孕酮受体基因多态性在宁夏回、汉族人群中的分布特征

目的:探讨孕酮受体基因(PGR基因)rs590688、rs1042838、rs11224592三个单核苷酸多态性(SNP)位点在宁夏回、汉族人群的分布特征并与1000Genomes网站上公布的其他群体分布频率进行比较分析。方法:采用TaqMan探针基因分型方法分析宁夏回、汉族人群867例(回族335例,汉族532例)PGR 3个SNPs位点rs590688、rs1042838、rs11224592基因型及等位基因频率的分布情况。结果:宁夏回、汉族人群PGR基因rs590688和rs1042838两个位点基因型及等位基因频率分布差异无统计学意义;rs11224592位点基因型及等位基因频率在宁夏回、汉族人群的分布差异有统计学意义;3个SNP位点的基因型及等位基因分布频率在男、女性别间差异无统计学意义。宁夏人群PGR基因rs590688、rs1042838、rs11224592位点基因型及等位基因分布频率与1000Genomes网站公布的其他群体相比较,rs590688位点与欧洲人群及非洲人群差异均有统计学意义;rs1042838位点与欧洲人群的差异有统计学意义;rs11224592位点与非洲人群的差异有统计学意义。结论:PGR基因rs590688、rs1042838、rs11224592位点基因型及等位基因频率在宁夏回、汉族人群的分布中,rs590688和rs1042838两个位点的分布无民族差异;rs11224592位点的分布具有民族差异;3个SNP位点的分布无性别差异。PGR 3个SNP位点基因型及等位基因频率在不同种族和地区的分布不同。     

湖北土家族群体15个短串联重复序列基因座遗传多态性

目的 调查湖北地区土家族人群15个短串联重复序列(short tandem repeat,STR)基因座遗传多态性分布和群体遗传学数据,比较分析湖北土家族与重庆土家族等位基因的分布频率.方法 采用毛细管电泳技术和五色荧光复合扩增的方法,对湖北土家族333名无关个体的15个STR基因座进行基因分型.结果 共检出151个等位基因,多于重庆土家族的等位基因检出数(141个),其频率分布在0.002～0.498之间.经Statistical genetics软件分析,各基因座的群体基因型分布符合Hardy-Weinberg平衡(P＞0.05).15个STR基因座的杂合度在0.652～0.867之间,个体识别力在0.802～0.971之间,累积个体识别力大于0.9 999 999;非父排除率在0.357～0.730之间,累积非父排除率为0.9 999 997;多态信息含量在0.57～0.87之间.结论 建立了湖北土家族人群的STR基因座的群体资料,为土家族人群的群体遗传学研究、法医个人识别、亲子鉴定提供了基础数据;湖北土家族与重庆土家族亲缘关系相近,等位基因频率差异无统计学意义(P＞0.05),但在等位基因检出数及部分基因分布频率上仍存在差异.     

新疆汉族和维吾尔族健康人群VKORC1启动子区基因多态性研究

目的了解VKORC1—1639A／G基因多态性在新疆汉族和维吾尔健康人群中的分布及其与国外其他不同民族之间的差异。方法采用PCR—RFLP技术对205名汉族和204名维吾尔族乌鲁木齐地区体检健康者VKORC1—1639A／G基因多态性进行检测，计算其基因型和等位基因频率，并与国外多个民族VKORC1—1639A／G基因多态性分布进行比较。结果新疆汉族和维吾尔族健康人群中共检测到2种等位基因：A和G。汉族A和G等位基因频率分别为87％和13％，维吾尔族A和G等位基冈频率分别为62％和38％。新疆汉族和维吾尔族健康人群VKORC1—1639A／G基因多态性共检测到3种基因型，新疆汉族健康人群以AA基因型常见，基因型频率74％。其次是AG基因型，基因型频率分别为26％。GG基因型的个体仅检测到1例，基因型频率小于1。新疆维吾尔族健康人群以AG基因型常见，基因型频率58％。其次是AA基因型，基因型频率分别为33％。GG基因型频率为9％。结论新疆汉族VKORC1—1639A／G基因多态性以AA基因型为主。维吾尔族VKORC1—1639A／G基因多态性以AG基因型为主，新疆汉族VKORC1—1639A／G基因多态性分布与维吾尔族人群和欧美人群存在较大差异。新疆维吾尔族人群VKORC1—1639A／G基因多态性分布与欧关人群接近。     

贵州三个民族亚甲基四氢叶酸还原酶基因的遗传多态性

目的研究贵州汉族、布依族、苗族亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase，MTHFR)基因多态性，为贵州少数民族基因多态性数据库的建立提供相关数据。方法应用聚合酶链反应及限制性片段长度多态性检测贵州荔波汉族、布依族、雷山苗族MTHFR基因两个单核苷酸(677及1298位)多态位点的基因频率及基因型频率。结果汉族、布依族、苗族MTHFR677位T等位基因的分布频率分别是22．8％，16．1％，10．6％，MTHFR1298位C等位基因的分布频率分别是28．9％，39．1％，48．7％，677CT／1298AC双杂合子的分布频率分别是16．66％，22．7％，11．1％。在苗族还发现1例677TT／1298CC双纯合子。结论．MTHFR C677T和A1298C多态性存在群体差异；贵州雷山苗族、荔波布依族．MTHFR 1298位有较高的C等位基因频率，贵州雷山苗族MTHFR 1298位C等位基因频率是目前文献报道最高的民族。     

中国汉族、维吾尔族和哈萨克族人MDR1-C3435T基因多态性研究

目的了解MDR1-C3435T的基因多态性在汉族、维吾尔族和哈萨克族健康人群中的分布差异,为临床用药提供参考。方法用PCR-RFLP的方法检测汉族、维吾尔族和哈萨克族MDR1-C3435T等位基因突变位点的分布情况。计算各民族基因型频率,并与已报道的其他民族的基因型频率和等位基因频率进行比较。结果 MDR1-C3435T基因在汉族、维吾尔族和哈萨克族三个民族中最常见的等位基因是MDR1-3435T,频率依次为汉族43.3%、维吾尔族58.0%和哈萨克族56.9%。等位基因MDR1-3435T在汉族中的发生频率显著低于维吾尔族和哈萨克族,而突变频率在维吾尔族和哈萨克族之间则无明显差异。汉族的基因突变发生频率与其他亚洲人相似,与高加索人差异显著;而维吾尔族和哈萨克族的发生频率介于亚洲人和高加索人之间。结论汉族、维吾尔族和哈萨克族的MDR1-C3435T基因型分布有明显的差异,对临床用药将产生显著影响。     

中国藏族人群具有低CCR5Δ32、高CCR2b-64I突变型基因频率

目的：调查CCR5△32、CCR5m303、CCR2b-64I和SDF1－3’A等人类免疫缺陷病毒（humanimmune deficiency virus-1,HIV-1)相关的等位基因在中国藏族人群中的频率和分布情况。方法：随机采集血样,提取基因组DNA,经PCR或PCR－RFLP分析,计算突变形基因频率,并对其群体分布、性别分布以及其相关性进行统计学分析。结果：发现藏族人的CCR5△32和CCR5m303突变型基因频率均小于0．15％;SDF1－3’A和CCR2b-64I突变型基因频率分别为19．24％和29．42％。4种突变等位基因群体分布均符合Hardy-Weinberg平衡,性别之间差异无显著性。虽然中国藏族人群CCR2b-64I的突变型基因频率较高,但CCR5△32和SDF1－3’A的突变型基因频率低,提示中国藏族人群很可能在遗传上是HIV－1易感的人群。结论：中国藏族人群与西方白人相比可能具有低CCR5△32和高CCR2b-64I等位基因突变频率。     

Distribution of two HIV-1-resistant polymorphisms (SDF1-3'A and CCR2-64I alleles) in the Polish population

Chemokine receptors (CCR2 and CXCR4) are used as coreceptors for entry of human immunodeficiency virus (HIV) into the target cells. Mutations in CCR2 (CCR2-64I) and stromal-derived factor SDF1 (SDF1-3'A), the primary ligand for CXCR4, exhibited a protective effect against the onset of acquired immune deficiency syndrome (AIDS). The frequency of the SDF1-3'A and CCR2-64I alleles were determined in blood donors from 16 provinces, covering the entire territory of Poland. Of 1063 individuals, 274 (25.8%) were carriers of the SDF1-3'A allele; 36 of them (3.4%) were homozygotes (SDF-3'A/A) while 238 (22.4%) were heterozygotes (SDF-3'G/A), resulting in a 14.6% frequency of the SDF1-3'A allele. Moreover, in the same group of individuals, 234 (22.0%) carried the CCR2-64I allele; 6 of them (0.6%) were homozygotes (CCR2-64I/I), and 228 (21.4%) were heterozygotes (CCR2-64V/I), resulting in an 11.3% frequency of the CCR2-64I allele. The highest frequencies of the SDF1-3'A allele were found in the northeastern provinces and in one of the western provinces of Poland. In contrast, allelic frequencies of CCR2-64I varied slightly among different provinces. The different pattern of prevalence of the SDF1-3'A and CCR2-64I alleles in Poland might suggest that the CCR2-64I allele was spread much earlier than the SDF1-3'A allele in the population of Poland.     

Stromal cell-derived factor 1 (SDF1) genetic polymorphism in a sample of healthy individuals, seronegative individuals exposed to human immunodeficiency virus type 1 (HIV-1) and patients infected with HIV-1 from the Brazilian population

The interaction of viral and host factors is believed to determine not only the risk for initial human immunodeficiency virus type 1 (HIV-1) acquisition but also the course of the infection. Genetic polymorphisms in the chemokine receptors and their ligands were related to the susceptibility and resistance to HIV-1 infection. A polymorphism in the conserved 3' untranslated region of the stromal cell-derived factor-1 (SDF1) gene, which encodes a ligand of the CXCR4 receptor, has been related either to delayed progression to AIDS or to rapid disease progression and death. Global, regional, and ethnic distributions of frequencies of SDF1 genotypes and of the SDF1-3'A allele vary significantly. Although the HIV-1 epidemic is increasing in Brazil, little information about the frequencies of host genetic mutations related to HIV/AIDS resistance in the Brazilian population has been reported. To address this question, this study was carried out in order to determine the frequencies of the SDF1 polymorphism and the SDF1-3'A allele on 1061 genomic DNA samples purified from peripheral blood cells of 136 healthy individuals (group 1), 147 HIV-1-exposed seronegative individuals (group 2), 161 HIV-1-infected asymptomatic individuals and with CD4(+) T-cells count 350 mm(-3) (group 3), and 617 HIV-1-infected individuals with AIDS and/or CD4(+) T-cells count < 350 mm(-3) (group 4). The frequencies of the SDF1-3'A homozygous mutation were 3.7%, 6.1%, 4.3%, and 5.3% among groups 1, 2, 3, and 4, respectively (P = 0.5120). The overall frequency of the SDF1-3'A allele was 0. 1984 and did not differ among the four groups (P = 0.2744). The results underscore the global distribution of the SDF1 polymorphism and the hypothesis that the SDF1-3'A allele, itself, may not be sufficient to prevent the risk of HIV-1 infection and may be not related to the progression of the disease in the Brazilian population.     

Distribution of CCR5delta32, CCR2-64I and SDF1-3'A and plasma levels of SDF-1 in HIV-1 seronegative North Indians.

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.     

Distribution of HIV/AIDS protective SDF1, CCR5 and CCR2 gene variants within Cretan population.

An interesting finding in the epidemiology of human immunodeficiency virus (HIV) infection is that certain mutations in genes coding for chemokine receptors and their ligands may confer resistance to HIV-1 infection and/or AIDS progression. The mutations most frequently studied are the CCR5-delta32, CCR2-64I and SDF1-3'A. We examined the frequency of the above polymorphisms within the Cretan population, evaluating their contribution to a protective genetic background against HIV infection and progression. Two hundred blood samples were recruited at random among prospective blood donors from Crete. Genotyping was initially performed by polymerase chain reaction (PCR) analysis. CCR2 and SDF-1 PCR-amplified genomic regions were further subjected to restriction fragment length polymorphism (RFLP) analysis for genotype determination. The CCR5-delta32 allele frequency among our study group was 3.25%, although no respective homozygous samples were detected. The screening for the CCR2-64I polymorphism yielded 39 heterozygous (19.5%) and 4 homozygous (2%) subjects, revealing a CCR2-64I allele frequency of 11.75%. Among our 200 PCR-RFLP analysed samples, 73 (36.5%) were found heterozygous and 23 (11.5%) homozygous for the SDF1-3'A mutant variant. The allele frequency of the above polymorphism reached 29.75%. The frequency of the CCR5-delta32 allele among our study population seems to be remarkably lower compared to previously reported frequencies in other Caucasian groups. However, the SDF1-3'A allele frequency shows significantly higher distribution profiles within our study group compared to those observed in other Caucasian-European populations. The indicated difference could be attributed to the increased homogeneity of our population, which is well balanced and dispersed over a small geographical area. Since this polymorphism is related with delayed progression from HIV infection to AIDS, it could be used for prognostic genotyping in HIV infected Cretan individuals.     

Population survey of CCR5 delta32, CCR5 m303, CCR2b 64I,and SDF1 3'A allele frequencies in indigenous Chinese healthy individuals,and in HIV-1-infected and HIV-1-uninfected individuals in HIV-1 risk groups

The aim of this study is to determine in indigenous Chinese ethnic groups the frequencies of the chemokine (SDF1 3'A) and chemokine receptors (CCR5 delta32, CCR5 m303, and CCR2b 64I) HIV-1/AIDS restriction alleles. The study includes two cohorts; the first comprised 3165 indigenous healthy subjects representing eight ethnic groups: Han (n = 1406), Uygur (n = 316), Mongolia (n = 134), Hui (n = 386), Tibetan (n = 330), Zhuang (n = 378), Dai (n = 101), and Jingbo (n =114). The second cohort consisted of 330 HIV-1-infected (86 subjects infected by sexual transmission and 198 subjects infected by HIV-1-contaminated blood or by sharing injection equipment; the remaining 46 subjects said nothing about HIV-1 transmission) and 474 HIV-1-uninfected Han Chinese belonging to one of two HIV-1 high-risk groups: intravenous drug users (n = 215) and individuals with sexually transmitted diseases (n = 259). Genotypes for the four genes were obtained using PCR (CCR5 delta32) or PCR-restriction fragment length polymorphism. Randomly selected amplified PCR products were further confirmed by direct DNA sequencing. The variant allele frequencies were determined to be 0% to 3.48% for CCR5 delta32, 0% for CCR5 m303, 16.23% to 28.79% for CCR2b 64I, and 17.70% to 27.76% for SDF1 3'A in Chinese healthy individuals from eight ethnic groups. These findings show that allele frequencies differ among the eight Chinese ethnic groups for CCR5 delta32, CCR2b 64I, and SDF1 3'A and that the CCR5 m303 and CCR5 delta32 mutant alleles were absent or infrequent in Chinese, which may be helpful for studies of specific anti-HIV-1 vaccine trials and coreceptor inhibitor drug targets in Chinese populations. Furthermore, we observed no significant differences in allele or genotypic frequencies between HIV-1-infected and HIV-1-uninfected groups from the Han ethnic group. Our finding is the first reporting that there is likely no effect of the examined polymorphisms in our study on HIV-1 transmission in the Chinese Han population, However, the genetic effects of these and other AIDS-modifying polymorphisms on the pathogenesis and clinical outcome of HIV-1/AIDS diseases is under investigation in Chinese populations.     

Distribution of CCR2-64I and SDF1-3'A alleles and HIV status in 7 ethnic populations of Cameroon

Limited information is available on the prevalence among rural Africans of host genetic polymorphisms conferring resistance to HIV-1 infection or slowing HIV disease progression. We report the allelic frequencies of the AIDS-related polymorphisms CCR2-64I, SDF1-3'A, and CCR5-Delta32 in 321 volunteers from 7 ethnic groups in Cameroon. Allelic frequencies differed among the 7 ethnic groups, ranging from 10.8% to 31.3% for CCR2-64I and 0.0% to 7.1% for SDF1-3'A. No CCR5-Delta32 alleles were found. HIV seroprevalence was 6.9% in the total population and peaked at younger ages in girls and women than in boys and men. Among 15- to 54-year-olds, HIV seroprevalence varied from 2.0% to 11.1% among the village populations. Conditional logistic regression analysis using data from boys and men aged 15 to 54 years showed the number of CCR2-64I alleles to be a significant risk factor for HIV seropositivity (odds ratio per allele adjusted for age and matched on ethnic group = 6.3, 95% confidence interval: 1.3-30.3); this association was not found in women. The findings are consistent with the hypothesis that CCR2-64I alleles may delay HIV disease progression without affecting susceptibility to infection among men. We did not observe this relation among women, and other factors, such as multiple pregnancies or maternal stressors (eg, breastfeeding), may have masked any protective effect of CCR2-64I alleles. Further study of this issue among women is warranted. SDF1-3'A did not differ between HIV-seropositive and HIV-seronegative individuals but was associated with increasing age among HIV-seronegative women, suggesting a protective effect against HIV-1 infection.     

Frequencies of SDF-1 chemokine, CCR-5, and CCR-2 chemokine receptor gene alleles conferring resistance to human immunodeficiency virus type 1 and AIDS in Kuwaitis

The frequencies of three mutations conferring resistance to HIV/AIDS were determined in a population sample of native Kuwaitis. The CCR2-641, SDF1-3'A, and CCR5-m303 mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) tests using restriction endonucleases Bsa BI, Msp I, and Hinc II, respectively. The frequency of the mutant alleles were: for CCR2-641, 0.1195 (95% CI 0.0801-0.1694); for SDF1-3'A, 0.2593 (95% CI 0.2024-0.3231), and for CCR5-m303, less than 0.0025. Thus, the CCR2-641 and especially SDF1-3'A mutations are sufficiently common in Arabs and can be used for prognostic genotyping in HIV-infected individuals from the Gulf countries.     

The effect of stromal cell-derived factor 1 (SDF1/CXCL12) genetic polymorphism on HIV-1 disease progression

The human immunodeficiency virus type 1 (HIV-1) epidemic is increasing in Brazil, and little information has been reported about the genetic host factors related to HIV-1 infection in the Brazilian population. A polymorphism in the conserved 3' untranslated region of the stromal cell-derived factor 1 (SDF1/CXCL12) gene has been related either to resistance to HIV-1 infection and delayed progression to AIDS or to rapid disease progression and death. A longitudinal study was conducted to evaluate the association of the SDF1 polymorphism and the progression of HIV-1 infection in 161 asymptomatic patients infected with HIV-1 (ASYMPT) and 617 patients with AIDS (SYMPT) from Londrina and the surrounding region, southern Brazil. The endpoints used were the development of AIDS, death, and the slopes of the CD4+ T cell counts and HIV-1 RNA plasma levels. Among the 161 ASYMPT patients, all of the 7 patients (4.3%) homozygous for the mutation remained asymptomatic (p=0.1906); 6 of them had not initiated antiretroviral therapy. Among the 617 patients with AIDS, 40 (6.5%) progressed to death. Of these, 33/388 (8.5%) did not have the SDF1-3'A allele, 6/196 (3.1%) were heterozygous and 1/33 (3.0%) was homozygous for the SDF1-3'A allele (p=0.029). The SDF1 genotypes were not associated with the surrogate markers of HIV-1 disease progression such as the CD4+ T cell decline and plasma HIV-1 RNA levels. The results observed in this study support the hypothesis that the mutation of SDF1-3'A could have a possible late-stage protective effect on HIV-1 disease progression in the Brazilian population.     

Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3'A, CCR2-641, and CCR5-delta32) in global populations

Chemokine receptors (CCR5, CXCR4 and CCR2) have been shown to be important co-receptors for HIV infection. Mutations at CCR5 (CCR5-delta2), CCR2 (CCR2-641), and stromal-derived factor SDF1 (SDF1-3'A), a primary ligand for CXCR4, are known to have protective effects against HIV-1 infection and the onset of AIDS symptoms. We studied the three-locus genotype frequency distributions in 70worldwide populations from a sample of 2341 individuals without any known history of HIV-1 infection and AIDS symptoms. From these data, we estimated the risk of AIDS onset (relative hazard, RH) of each population. This survey shows that the substantial allele frequency differences of each of these mutations translate into an extensive variation in relative hazards for AIDS in worldwide populations. However, no evidence of natural selection against the mutant gene carriers is detected. Finally, the combined three-locus genotype data predict the highest relative hazard (RH) in South-East Asia and Africa where AIDS is known to be more prevalent.