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Role of CCR5, CCR2 and SDF-1 gene polymorphisms in a population of HIV-1 infected individuals.
J Biol Regul Homeost Agents. 2001 Jul-Sep; 15(3):265-71.JB

Abstract

The finding that in addition to CD4 molecule HIV-1 uses, CCR5 or CXCR4 receptors to enter target cells prompted the research to identify polymorphisms in coreceptor genes affecting disease progression. In this study we analyzed the prevalence of CCR5-delta32, CCR2-641 and SDF1-3'A alleles in a highly selected group of 42 Long-Term Nonprogressors (LTNPs) compared to 112 subjects with a typical course of HIV-1 infection (TPs) and 117 healthy controls (HCs). In addition, we correlated CCR5, CCR2 and SDF-1 genotypes with molecular indexes of HIV-1 replication, cell-free RNA and both unspliced (US) and multiply spliced (MS) intracellular transcripts, to investigate the role of the mutant alleles in determining a long-term nonprogressive course of HIV-1 disease. Our results indicate a significantly higher prevalence of CCR5-delta32 allele in LTNPs compared to TPs (p=0.0434), while the proportions of CCR2-64I and SDF1-3'A alleles were comparable between the two groups. However, SDF-1 wild type LTNP subjects showed significantly lower levels of HIV-1 genomic RNA, US and MS transcripts than SDF1-3'A heterozygous ones (p=0.0021, 0.016, 0.0031, respectively), whereas both CCR5 and CCR2 wild type individuals had similar rates of viral replication compared to CCR5-delta32 and CCR2-64I heterozygous ones. CCR5, CCR2 and SDF-1 combined genotypes were also studied and this analysis did not identify a specific protective cluster of alleles in LTNPs. Taken together, our results indicate that genetic background involving CCR5, CCR2 and SDF-1 alleles may play a limited role in the natural history of HIV-1 infection.

Authors+Show Affiliations

Institute of Infectious and Tropical Diseases, University of Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11693435

Citation

Mazzucchelli, R, et al. "Role of CCR5, CCR2 and SDF-1 Gene Polymorphisms in a Population of HIV-1 Infected Individuals." Journal of Biological Regulators and Homeostatic Agents, vol. 15, no. 3, 2001, pp. 265-71.
Mazzucchelli R, Corvasce S, Violin M, et al. Role of CCR5, CCR2 and SDF-1 gene polymorphisms in a population of HIV-1 infected individuals. J Biol Regul Homeost Agents. 2001;15(3):265-71.
Mazzucchelli, R., Corvasce, S., Violin, M., Riva, C., Bianchi, R., Dehò, L., Velleca, R., Cibella, J., Bada, M., Moroni, M., Galli, M., & Balotta, C. (2001). Role of CCR5, CCR2 and SDF-1 gene polymorphisms in a population of HIV-1 infected individuals. Journal of Biological Regulators and Homeostatic Agents, 15(3), 265-71.
Mazzucchelli R, et al. Role of CCR5, CCR2 and SDF-1 Gene Polymorphisms in a Population of HIV-1 Infected Individuals. J Biol Regul Homeost Agents. 2001;15(3):265-71. PubMed PMID: 11693435.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of CCR5, CCR2 and SDF-1 gene polymorphisms in a population of HIV-1 infected individuals. AU - Mazzucchelli,R, AU - Corvasce,S, AU - Violin,M, AU - Riva,C, AU - Bianchi,R, AU - Dehò,L, AU - Velleca,R, AU - Cibella,J, AU - Bada,M, AU - Moroni,M, AU - Galli,M, AU - Balotta,C, PY - 2001/11/6/pubmed PY - 2002/3/20/medline PY - 2001/11/6/entrez SP - 265 EP - 71 JF - Journal of biological regulators and homeostatic agents JO - J. Biol. Regul. Homeost. Agents VL - 15 IS - 3 N2 - The finding that in addition to CD4 molecule HIV-1 uses, CCR5 or CXCR4 receptors to enter target cells prompted the research to identify polymorphisms in coreceptor genes affecting disease progression. In this study we analyzed the prevalence of CCR5-delta32, CCR2-641 and SDF1-3'A alleles in a highly selected group of 42 Long-Term Nonprogressors (LTNPs) compared to 112 subjects with a typical course of HIV-1 infection (TPs) and 117 healthy controls (HCs). In addition, we correlated CCR5, CCR2 and SDF-1 genotypes with molecular indexes of HIV-1 replication, cell-free RNA and both unspliced (US) and multiply spliced (MS) intracellular transcripts, to investigate the role of the mutant alleles in determining a long-term nonprogressive course of HIV-1 disease. Our results indicate a significantly higher prevalence of CCR5-delta32 allele in LTNPs compared to TPs (p=0.0434), while the proportions of CCR2-64I and SDF1-3'A alleles were comparable between the two groups. However, SDF-1 wild type LTNP subjects showed significantly lower levels of HIV-1 genomic RNA, US and MS transcripts than SDF1-3'A heterozygous ones (p=0.0021, 0.016, 0.0031, respectively), whereas both CCR5 and CCR2 wild type individuals had similar rates of viral replication compared to CCR5-delta32 and CCR2-64I heterozygous ones. CCR5, CCR2 and SDF-1 combined genotypes were also studied and this analysis did not identify a specific protective cluster of alleles in LTNPs. Taken together, our results indicate that genetic background involving CCR5, CCR2 and SDF-1 alleles may play a limited role in the natural history of HIV-1 infection. SN - 0393-974X UR - https://www.unboundmedicine.com/medline/citation/11693435/Role_of_CCR5_CCR2_and_SDF_1_gene_polymorphisms_in_a_population_of_HIV_1_infected_individuals_ L2 - http://www.diseaseinfosearch.org/result/9735 DB - PRIME DP - Unbound Medicine ER -