title: Chemokine receptor CCR2b 64I polymorphism and its relation to CD4 T-cell counts and disease progression in a Danish cohort of HIV-infected individuals. Copenhagen AIDS cohort.
abstract: We have investigated the role of the recently described mutation in CCR2b named 64I in relation to HIV resistance, CD4 T-cell counts, and disease progression in Danish individuals by polymerase chain reaction (PCR)-based methods as well as sequenced full-length CXCR4 and CCR5 genes from HIV-infected long-term nonprogressors for possible mutations. In total, 215 Danish individuals were analyzed for 64I allele frequency; disease progression was followed in 105 HIV-1-positive homosexual Danish men from their first known positive HIV-1 test result and up to 11 years. In 87 individuals, the CD4 T-cell count was monitored closely. We found no significant difference in 64I allele frequency between HIV-1-seropositive persons (0.08), high-risk HIV-1-seronegative persons (0.11), and blood donors (0.06). No significant difference was observed in annual CD4 T-cell decline, CD4 T-cell counts at the time of AIDS, in AIDS-free survival as well as survival with AIDS, between 64I allele carriers and wild-type individuals. Among 9 long-term nonprogressors, 2 carried the 64I allele, while none of 9 fast progressors carried the 64I allele. However, this was not significantly different (p=.47). Long-term nonprogression could not be explained by CXCR4 polymorphism or other polymorphisms in the CCR5 gene than the CCR5delta32 allele. Furthermore, we were not able to detect any significant independent effect of the 64I allele on development to AIDS, overall survival, and annual CD4 T-cell decline in this cohort.
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospitals, Hvidovre, Denmark. jeo@biobase.dk
authors.forename: J
authors.initials: J
authors.lastname: Eugen-Olsen
authors.forename: A K
authors.initials: AK
authors.lastname: Iversen
authors.forename: T L
authors.initials: TL
authors.lastname: Benfield
authors.forename: U
authors.initials: U
authors.lastname: Koppelhus
authors.forename: P
authors.initials: P
authors.lastname: Garred
mesh_terms: D000483:Alleles; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D003718:Denmark; D018450:Disease Progression; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*; D015996:Survival Rate
chemical_list: C515334:CCR2 protein, human; D017931:DNA Primers; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine