CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro

Salkowitz, Janelle R.; Bruse, Shannon; Meyerson, Howard; Valdez, Hernán; Mosier, Donald E.; Harding, Clifford V.; Zimmerman, Peter A.; Lederman, Michael M.

doi:10.1016/s1521-6616(03)00147-5

Cited by 83 publications

(61 citation statements)

References 32 publications

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“…31,33 The implications of these findings require further exploration in this population, since no difference with HESNs was detected.…”

Section: Discussionmentioning

confidence: 92%

“…Finally, the GACAT haplotype was more frequent in HC than SP individuals; furthermore, this haplotype contains the 927T allele, which has been associated with slow AIDS progression in SPs and lower probability of becoming infected. 31,33 HHC was more frequent than HHE in the HESNs. Previously, Gonzalez et al reported that white, Asian, and Hispanic American populations exhibited a higher frequency of HHC than HHE, as in our HESN group, but contrary to what was observed in the HC and SP groups.…”

mentioning

confidence: 88%

“…33 These contradictory results could be due to other SNPs in the TGCAC haplotype overcoming the protective effect of the 303G allele. Finally, the GACAT haplotype was more frequent in HC than SP individuals; furthermore, this haplotype contains the 927T allele, which has been associated with slow AIDS progression in SPs and lower probability of becoming infected.…”

mentioning

confidence: 99%

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Influence ofCCR5andCCR2Genetic Variants in the Resistance/Susceptibility to HIV in Serodiscordant Couples from Colombia

Zapata

Aguilar-Jiménez

Pineda-Trujillo

et al. 2013

AIDS Research and Human Retroviruses

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The main genetic factor related to HIV-1 resistance is the CCR5-D32 mutation; however, the homozygous genotype is uncommon. The CCR5-D32 mutation along with single nucleotide polymorphisms (SNPs) in the CCR5 promoter and the CCR2-V64I mutation have been included in seven human haplogroups (HH) previously associated with resistance/susceptibility to HIV-1 infection and different rates of AIDS progression. Here, we determined the association of the CCR5 promoter SNPs, the CCR5-D32 mutation, CCR2-V64I SNP, and HH frequencies with resistance/susceptibility to HIV-1 infection in a cohort of HIV-1-serodiscordant couples from Colombia. Seventy HIV-1-exposed, but seronegative (HESN) individuals, 57 seropositives (SP), and 112 healthy controls (HC) were included. The CCR5-D32 mutation and CCR2-V64I SNP were identified by PCR, and the CCR5 promoter SNPs were evaluated by sequencing. None of the individuals exhibited a homozygous D32 genotype; the CCR2-I allele was more frequent in HESN (34%) than HC (23%) ( p = 0.039, OR = 1.672). The frequency of the 29G allele was higher in SP than HC ( p = 0.003, OR = 3). HHF2 showed a higher frequency in HC (19%) than SP (9%) ( p = 0.027), while HHG1 was more frequent in SP (11.1%) than in HC (4.2%) ( p = 0.019). The AGACCAC-CCR2-I-CCR5 wild-type haplotype showed a higher frequency in SP (14.2%) than in HC (3.7%) ( p = 0.001). In conclusion, the CCR5-D32 allele is not responsible for HIV-1 resistance in this HESN group; however, the CCR2-I allele could be protective, while the 29G allele might increase the likelihood of acquiring HIV-1 infection. HHG1 and the AGACCAC-CCR2-I-CCR5 wild-type haplotype might promote HIV-1 infection while HHF2 might be related to resistance. However, additional studies are required to evaluate the implications of these findings.

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“…31,33 The implications of these findings require further exploration in this population, since no difference with HESNs was detected.…”

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 88%

mentioning

confidence: 99%

See 1 more Smart Citation

Influence ofCCR5andCCR2Genetic Variants in the Resistance/Susceptibility to HIV in Serodiscordant Couples from Colombia

Zapata

Aguilar-Jiménez

Pineda-Trujillo

et al. 2013

AIDS Research and Human Retroviruses

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“…The CCR5 P1 allele, a composite haplotype comprising 13 distinct SNP alleles in the upstream promoter region of CCR5, confers recessive more rapid progression to AIDS 34,35 . Analysis of CCR5 promoter alleles found no quantitative differences in luciferase transcription, HIV-1 binding or HIV-1 infectivity, although the alleles influence CCR5 abundance on lymphoid cells 36,37 . Further, oligonucleotides that define the CCR5 P1 allele showed allele-specific recognition of nuclear transcription factors belonging to the cREL family, a result that suggests, but does not prove, that CCR5 promoter alleles could differentially react and respond to transcription factors in different cell types 37 .…”

Section: Mechanism Of Action For Argsmentioning

confidence: 89%

Human genes that limit AIDS

2004

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“…This association is believed to occur because persons homozygous for this haplotype have greater levels of expression of the chemokine receptor and HIV coreceptor, CCR5. 17,18 This high-expressing CCR5 genotype, termed 59029 A/A, 19 P1/P1, 20 Ϫ2459A/A, 21 or HHE/HHE, 22 also has been associated with renal transplantation outcomes. 23 Here we used 4 variants of the CCR5 gene to define the high-expressing haplotype, which in this study we term CCR5 H1.…”

Section: Introductionmentioning

confidence: 99%

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

McDermott

Conway

Wang

et al. 2010

Blood

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Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen-matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P ‫؍‬ .005) and overall survival (P ‫؍‬ .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P ‫؍‬ .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. (Blood.

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CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro

Abstract: The common CCR5 promoter polymorphism at position -2459 (A/G) has been associated with differences in the rate of progression to AIDS, where HIV-1-infected individuals with the CCR5

Cited by 83 publications

References 32 publications

Influence ofCCR5andCCR2Genetic Variants in the Resistance/Susceptibility to HIV in Serodiscordant Couples from Colombia

Influence ofCCR5andCCR2Genetic Variants in the Resistance/Susceptibility to HIV in Serodiscordant Couples from Colombia

Human genes that limit AIDS

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

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