Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression

Science

Volumn 277, Issue 5328, 1997, Pages 959-965

  Smith, Michael W ^a   Dean, Michael ^a   Carrington, Mary ^a   Winkler, Cheryl ^a   Huttley, Gavin A ^a   Lomb, Deborah A ^a   Goedert, James J ^a   O'Brien, Thomas R ^a   Jacobson, Lisa P ^a   Kaslow, Richard ^a   Buchbinder, Susan ^a   Vittinghoff, Eric ^a   Vlahov, David ^a   Hoots, Keith ^a   Hilgartner, Margaret W ^a   O'Brien, Stephen J ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR; VIRUS RECEPTOR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ARTICLE; CONTROLLED STUDY; DISEASE COURSE; GENE FREQUENCY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; MUTATION; PRIORITY JOURNAL; RECEPTOR GENE;

ACQUIRED IMMUNODEFICIENCY SYNDROME; AFRICAN CONTINENTAL ANCESTRY GROUP; COHORT STUDIES; DISEASE PROGRESSION; EUROPEAN CONTINENTAL ANCESTRY GROUP; GENOTYPE; HAPLOTYPES; HETEROZYGOTE; HIV INFECTIONS; HIV-1; HUMANS; MUTATION; POLYMERASE CHAIN REACTION; POLYMORPHISM, RESTRICTION FRAGMENT LENGTH; POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL; PROPORTIONAL HAZARDS MODELS; RECEPTORS, CCR5; RECEPTORS, CHEMOKINE; RECEPTORS, CYTOKINE; RECEPTORS, HIV; SURVIVAL ANALYSIS;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 0030861904     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.277.5328.959     Document Type: Article

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44. The coding region of the CCR2 gene was amplified with primers CCR2F3: 5′ ATGCT GTCCA CATCT CGTTC and CCR2R3: 5′ CCCAA AGACC CACTC ATTTG (1 to 327 bp); CCR2F4: 5′ ATTAC TCTCC CATTG TGGGC and CCR2R4: 5′ GGAAA TTATT CCATC CTCGTG (277 to 604 bp); CCR2F1: 5′ TTCTG TTTAT GTCTG TGGCC and CCR2R6: 5′ GATTG ATGCA GCAGT GAGTC (555 to 904 bp); and CCR2F5: 5′ CCAAG CCACG CAGGT GACAG and CCR2R5: 5′ TTATA AACCA GCCGA GACTT (852 to 1083 bp). The products were resolved on 6% acrylamide gels (37.5:1 acrylamide:bis-acrylamide) containing 10% glycerol at room temperature. The entire CCR2 coding region was examined by SSCP in 127 individuals. One common synonymous nucleotide substitution was discovered (N260N; f = 0.46), and three additional variants (CCR2: V52V, P47L, and S87A) were found in fewer than 1% of chromosomes. CCR2-641 homozygotes (one Caucasian and one African American) were sequenced through the entire coding region of CCR2 (including the CCR2A exon) and CCR5, as well as 500 bp of the upstream region of both genes. No nucleotide alterations were identified. More than 100 individuals have been screened by SSCP across the CCR5 gene. A total of 16 additional variants in the coding region have been identified (M. Carrington et al., in preparation). All of these variants are rare (≤4%) and none is found exclusively on the CCR2-641 haplotype.
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75. We gratefully acknowledge the patients, their families, and clinicians who have participated in the ALIVE, MACS, MHCS, HGDS, and SFCC cohort studies. We thank R. Boaze, R. Byrd, S. Cevario, B. Gerrard, P. Lloyd, M. McNally, M. Malasky, S. Shrestha, E. Topper, and M. Weedon for technical assistance, and S. Edelstein, A. Munoz, S. Donfield, E. Gomperts, J, Giorgi, and J. Oppenheim for helpful discussions. The Frederick Biomedical Supercomputing Center provided computational resources used in some of our analyses. Additional analyses and data mentioned here can be inspected at rex.n-ci.nih.gov/RESEARCH/basicyigd/front_page.htm.