Effects of CCR5-Δ32 and CCR2-64I alleles on HIV-1 disease progression

Mulherin, Stephanie A.; O’Brien, Thomas R.; Ioannidis, John P. A.; Goedert, James J.; Buchbinder, Susan; Coutinho, Roel A.; Jamieson, Beth D.; Meyer, Laurence; Michael, Nelson L.; Pantaleo, Giuseppe; Rizzardi, Gian-Paolo; Schuitemaker, Hanneke; Sheppard, Haynes W.; Théodorou, Ioannis; Vlahov, David; Rosenberg, Philip S.

doi:10.1097/00002030-200302140-00012

Cited by 85 publications

(34 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies have shown correlations between disease progression and the CCR2-64 I/V amino acid substitution and between CCR5 promoter haplotype/haplotype combinations (diplotype) [10,19,[23][24][25][26][27][28]. We were unable to demonstrate any relationship between these diplotypes and the in vitro phenotype; however, these additional analyses may have been limited by the small numbers of individuals in the diplotype in vitro phenotype categories observed in this study.…”

Section: Resultscontrasting

confidence: 67%

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

Salkowitz

Bruse

Meyerson

et al. 2003

Clinical Immunology

View full text Add to dashboard Cite

show abstract

Section: Resultscontrasting

confidence: 67%

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

Salkowitz

Bruse

Meyerson

et al. 2003

Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Although the CCR2-64I polymorphic variant has been reported to be protective in the development and progression of inflammatory diseases such as AIDS (Ioannidis et al, 2001;Mulherin et al, 2003), multiple sclerosis (Miyagishi et al, 2003), and development of breast cancer and cervical cancer (Zafiropoulos et al, 2004;Coelho et al, 2005), in our study this variant seems to be a risk factor for the development of bladder cancer.…”

Section: Discussioncontrasting

confidence: 64%

CCR2-64I is a risk factor for development of bladder cancer

Narter

Ağaçhan²,

Sözen³

et al. 2010

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Chemokines are potent proinflammatory cytokines that are implicated in numerous inflammatory diseases. Proinflammatory gene polymorphisms lead to variations in the production and concentration of inflammatory proteins. We investigated a possible association between polymorphisms in chemokine and chemokine receptor genes (MCP-1 A-2518G and CCR2-V64I) and bladder cancer risk. Genotypes were determined by PCR-RFLP assays in 72 bladder cancer patients and 76 unrelated age-matched healthy controls. There were significant differences in the frequencies of the MCP-1 A-2518G (P = 0.012) and CCR2-V64I genotypes (P = 0.004) between the controls and patients. The MCP-1 A-2518G GG genotype frequencies for controls and cases were 0.039 and 0.11, respectively; individuals who had the GG genotype had a 3-fold increased risk of bladder cancer (P = 0.08). The CCR2-64I/64I genotype frequencies for controls and cases were 0.02 and 0.13, respectively; subjects carrying the 64I/64I genotype had a 5.9-fold increased risk of bladder cancer compared to the other genotypes. Individuals carrying the CCR2-V64I heterozygote or homozygous variant genotype (64I/64I + wt/64I) had a 2.9-fold increased risk of bladder cancer compared with the wild-type genotype (wt/wt). CCR2-V64I heterozygote or homozygous wild-type genotype (wt/wt + wt/64I) frequencies were significantly decreased in the patient group compared with controls. We conclude that CCR2-64I is a new risk factor for bladder cancer.

show abstract

“…Published data demonstrate a disease-retarding effect of the CCR5 ⌬32/wt genotype in HIV-1-infected individuals (5,17,38,39,45) but are conflicting as to whether ⌬32 heterozygosity is associated with relative resistance to HIV-1 transmission (7,13,14,31,37,49,61). Our findings here demonstrate that a single ⌬32 allele exerts a protective effect against viral transmission only if it occurs combined with the Ϫ2459G allele in the CCR5 promoter region (33,35) on the other chromosome.…”

Section: Discussionmentioning

confidence: 99%

“…Since the discovery of these coreceptors, it has become well established that alterations in their gene expression and function can impact HIV-1 disease progression. For example, inheritance of the chemokine receptor (CR) polymorphisms CCR5 open reading frame (ORF) ⌬32, CCR5 promoter Ϫ2459 A-to-G, and CCR2 ORF 190 G-to-A (CCR2-64I) are associated with delayed development of the AIDS in HIV-1-infected patients (4,5,9,14,16,17,20,21,29,33,35,36,38,39,45,53,54). Moreover, individuals homozygous for the CCR5-⌬32 allele, comprising about 1% of the Caucasian population, have strongly reduced susceptibility to R5-dependent HIV-1 infection (7,26,49).…”

mentioning

confidence: 99%

Combined Effect of CCR5-Δ32 Heterozygosity and the CCR5 Promoter Polymorphism −2459 A/G on CCR5 Expression and Resistance to Human Immunodeficiency Virus Type 1 Transmission

Hladik

Liu²,

Speelmon

et al. 2005

J Virol

View full text Add to dashboard Cite

Exposed seronegative individuals (ES) with persistent high-risk sexual behavior may be less susceptible to human immunodeficiency virus type 1 (HIV-1) infection because they carry the chemokine receptor (CR) gene alleles CCR5 open reading frame (ORF) ⌬32, CCR5 promoter ؊2459G, or CCR2 ORF 64I (CCR2-64I), all of which have been found to diminish HIV-1 infectivity and/or disease progression. To investigate this, we determined the haplotypes for these three genetic loci in 93 ES and 247 low-risk control individuals. To test if protective haplotypes exert their effect by modulating CR expression, we measured the protein expression of CCR5 and CXCR4 on circulating CD4؉ T cells and CD14 ؉ monocytes in 71 ES and 92 controls. To avoid investigator bias, the analysis was performed without knowledge of each subject's risk and genotype. The CCR5 ؊2459G allele was significantly enriched in ES Caucasian men, who constituted the majority (84%) of the ES cohort, compared to the control Caucasian men (P ‫؍‬ 0.02). This increase was mostly attributable to a higher frequency of the ؊2459 A/G versus the ؊2459 A/A genotype in individuals heterozygous for the ⌬32 allele (P ‫؍‬ 0.012). No protective influence of the CCR2-64I allele was observed. The haplotypes CCR5 ORF ⌬32/CCR5 ؊2459A (in complete linkage disequilibrium) and CCR5 ORF wt/CCR5 ؊2459G had a cumulative negative effect on the expression of CCR5, since we measured significantly reduced CCR5 densities on both T-helper cells and monocytes only when both haplotypes were present. Densities of CCR5 on lymphocytes and monocytes were correlated (r ‫؍‬ 0.59; P < 0.0001), indicating concordance of CCR5 expression patterns across different cell types. We conclude that the CCR5 ORF ⌬32/wt-CCR5 ؊2459 A/G genotype combination offers an advantage in resisting sexual HIV-1 transmission and that this effect is mediated by a relative paucity of CCR5 on potential target cells of HIV-1.

show abstract

Effects of CCR5-Δ32 and CCR2-64I alleles on HIV-1 disease progression

Abstract: The protection against AIDS provided by CCR5-Delta32 is continuous during the course of infection. In contrast, the protection provided by CCR2-64I is greatest early in the course of infection.

Cited by 85 publications

References 35 publications

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

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

CCR2-64I is a risk factor for development of bladder cancer

Combined Effect of CCR5-Δ32 Heterozygosity and the CCR5 Promoter Polymorphism −2459 A/G on CCR5 Expression and Resistance to Human Immunodeficiency Virus Type 1 Transmission

Contact Info

Product

Resources

About