Protective Effect of CCR2-64I and Not of CCR5-Δ32 and SDF1-3´A in Pediatric HIV-1 Infection

Mangano, Andrea; Kopka, Julieta; Batalla, M. Rocamora; Bologna, Rosa; Sen, Luisa

doi:10.1097/00042560-200001010-00007

Cited by 36 publications

(38 citation statements)

References 36 publications

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“…The frequencies found in the indigenous populations are similar to those previously reported in populations of Asian origin (Smith et al 1997;Su et al 1999;Voevodin et al 1999;Mangano et al 2000;Iyer et al 2001;Wang et al 2001;Hong et al 2001;Ramana et al 2001). This observation is in accordance with the prevailing theory regarding the Asian origin of Amerindians (Silva et al 2002), as well as with the theory that CCR2-64I is an ancient mutation, since it is both common in Asians and present in other ethnic groups.…”

Section: Resultssupporting

confidence: 90%

“…However, progression to AIDS was observed to be two to three years longer in patients who were homozygous or heterozygous for the CCR2-64I mutation, as compared to those with wild-type CCR2 (Smith et al 1997). Subsequent studies investigating the distribution of the CCR2-64I mutation and allelic frequencies in different populations and ethnic groups worldwide (Martinson et al 2000;Struyf et al 2000;Mangano et al 2000;Barbouche et al 2001;Iyer et al 2001) have indicated that this mutation is most common in Asian populations (0.250), least common in Europeans (0.098), and of intermediate frequency (0.151) in African populations (Smith et al 1997). Subsequent studies, however, have shown contradictory values (Struyf et al 2000).…”

Section: Introductionmentioning

confidence: 99%

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Distribution of the CCR2-64I allele in three Brazilian ethnic groups

et al. 2003

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CCR2 is a member of the superfamily of seven transmembrane domain G protein-coupled receptors, the largest receptor superfamily in the human genome. CCR2 acts as a receptor for MCP-1 (CC chemokine) and as a co-receptor for HIV-1 cell-target entry. The gene encoding this receptor is mapped to the chromosome band 3p21. A G-to-A transition at position 190 characterizes the CCR2-64I mutation, causing valine to isoleucine substitution in codon 64. This mutation has been identified as an important factor for delaying progression to AIDS. Here, we determined the prevalence of this allele in three different Brazilian populations: 261 Amerindians inhabiting an isolated region in northern Brazil (82 samples from the Waiampi tribe, and 179 samples from the Tiriyó tribe); 89 German descendents from Joinville, a city in southern Brazil; and 305 individuals of predominantly African ancestry, from Salvador, a city in northeast Brazil. The CCR2-64I mutant allele was identified in 26% of the Tiryió and 30% of Waiampi samples, in 18% of the Joinville samples, and in 14% of the Salvador samples.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Distribution of the CCR2-64I allele in three Brazilian ethnic groups

et al. 2003

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“…In contrast, allele-D32 is rarely seen in Asian and African countries (Table 4). Finally, the frequency of the CCR5-D32 polymorphism in Latin American countries ranged from 0%, as observed in a Haitian population (Martinson et al, 2000), to 3.9%, a frequency reported in Argentina (Mangano et al, 2000).…”

Section: Discussionmentioning

confidence: 67%

Prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil

Ferreira-Fernandes

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Chemokines are low-molecular weight proteins that play a key role in inflammatory processes. Genomic variations in chemokine receptors are associated with the susceptibility to various diseases. Polymorphisms in chemokine receptor type 5 (CCR5)-D32 and CCR2-V64I are related to human immunodeficiency virus infection resistance, which has led to genetic association studies for several other diseases. Given the heterogeneous distribution of these polymorphisms in different global populations and within Brazilian populations, we analyzed the prevalence of CCR5-D32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. The study included 223 individuals from the general population of the city of Parnaíba, Piauí, who had a mean age of 73 years. Of these individuals, 37.2% were men 11711 CCR5-D32 and CCR2-V64I polymorphisms in Piauí, Brazil ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 11710-11718 (2015) and 62.8% were women. Polymorphisms were analyzed using DNA extracted from peripheral blood leukocytes by using polymerase chain reaction alone (CCR5-D32) or accompanied by restriction endonuclease digestion (CCR2-V64I). In both cases, the genotypes were determined using 8% polyacrylamide gel electrophoresis and silver nitrate staining. The population conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals were homozygous for allele-D32, which was present in 1.8% of the population, whereas allele-64I was present in 13.9% of the participants studied; 74.9% were homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and homozygous for the mutant allele, respectively. Additional studies are needed to investigate the relationship between these polymorphisms and disease etiopathogenesis in reference populations.

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“…Whereas CCR5 ORF ⌬32/⌬32 homozygosity occurs in just 1% of Caucasians, the CCR5 Ϫ2459 A/G plus CCR5 ORF ⌬32/wt or CCR2 ORF 64I/wt genotype combinations comprise approximately 5% each. However, the effects of these two genotype combinations on the susceptibility to HIV-1 infection in vivo have not been conclusively determined (6,7,13,14,17,22,27,30,31,37,49,53,55,61). Here, we have compared the frequencies of the CCR5 ORF wt/⌬32, CCR5 Ϫ2459A/G, and CCR2 ORF 64V/I alleles and allele combinations between the ES and the low-risk control group.…”

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

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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.

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Protective Effect of CCR2-64I and Not of CCR5-Δ32 and SDF1-3´A in Pediatric HIV-1 Infection

Cited by 36 publications

References 36 publications

Distribution of the CCR2-64I allele in three Brazilian ethnic groups

Distribution of the CCR2-64I allele in three Brazilian ethnic groups

Prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil

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

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