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PMID: 10518566 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 21 ·1999-10-12 ·Pages 12004-9

Gonzalez E, Bamshad M, Sato N, Mummidi S, Dhanda R, Catano G, Cabrera S, McBride M, Cao XH, Merrill G, O'Connell P, Bowden DW, Freedman BI, Anderson SA, Walter EA, Evans JS, Stephan KT, Clark RA, Tyagi S, Ahuja SS, Dolan MJ, Ahuja SK

Abstract

Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

MeSH Terms
Acquired Immunodeficiency Syndrome/genetics,metabolism Adolescent Adult Africa Aged Alleles Asia Biological Evolution Blacks/genetics Cohort Studies Disease Progression Female Genetic Variation Genotype HIV Seropositivity/epidemiology,genetics HIV-1 Haplotypes Humans Male Middle Aged Phylogeny Polymorphism, Restriction Fragment Length Racial Groups/genetics Receptors, CCR5/genetics Time Factors United States Whites/genetics
Chemicals
Receptors, CCR5
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Gonzalez E
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.
Bamshad M
Sato N
Mummidi S
Dhanda R
Catano G
Cabrera S
McBride M
Cao X H
Merrill G
O'Connell P
Bowden D W
Freedman B I
Anderson S A
Walter E A
Evans J S
Stephan K T
Clark R A
Tyagi S
Ahuja S S
Dolan M J
Ahuja S K
References (23)
23 references, click to expand
  1. Lack of evidence for human or simian T-lymphotropic viruses type III infection in pygmies.
    Lancet. 1986 Apr 12;1(8485):854 PMID: 2870333
  2. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes.
    Nature. 1999 Feb 4;397(6718):436-41 PMID: 9989410
  3. Seroepidemiologic, molecular, and phylogenetic analyses of simian T-cell leukemia viruses (STLV-I) from various naturally infected monkey species from central and western Africa.
    Virology. 1994 Jan;198(1):297-310 PMID: 8259665
  4. Infections among pygmies in the Eastern Province of Cameroon.
    Med Microbiol Immunol. 1993 Dec;182(6):281-4 PMID: 7907163
  5. Phylogenetic associations of human and simian T-cell leukemia/lymphotropic virus type I strains: evidence for interspecies transmission.
    J Virol. 1994 Apr;68(4):2693-707 PMID: 7908063
  6. Prevalence of hepatitis C virus and other blood-borne viruses in Pygmies and neighbouring Bantus in southern Cameroon.
    Trans R Soc Trop Med Hyg. 1995 Sep-Oct;89(5):484-6 PMID: 8560516
  7. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.
    Science. 1996 Sep 27;273(5283):1856-62 PMID: 8791590
  8. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression.
    Nat Med. 1996 Nov;2(11):1240-3 PMID: 8898752
  9. Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk.
    Mol Med. 1997 Jan;3(1):23-36 PMID: 9132277
  10. The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression.
    Nat Med. 1997 Mar;3(3):338-40 PMID: 9055864
  11. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.
    Science. 1997 Aug 15;277(5328):959-65 PMID: 9252328
  12. Co-receptors for HIV-1 entry.
    Curr Opin Immunol. 1997 Aug;9(4):551-62 PMID: 9287172
  13. The human CC chemokine receptor 5 (CCR5) gene. Multiple transcripts with 5'-end heterogeneity, dual promoter usage, and evidence for polymorphisms within the regulatory regions and noncoding exons.
    J Biol Chem. 1997 Dec 5;272(49):30662-71 PMID: 9388201
  14. Host factors in the pathogenesis of HIV disease.
    Immunol Rev. 1997 Oct;159:31-48 PMID: 9416501
  15. Chemokine-receptor polymorphisms: clarity or confusion for HIV-1 prognosis?
    Lancet. 1998 Jan 3;351(9095):2-3 PMID: 9433416
  16. CCR2 polymorphism and HIV disease. Swiss HIV Cohort.
    Nat Med. 1998 Mar;4(3):252-3 PMID: 9500580
  17. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation.
    Nat Med. 1998 Mar;4(3):350-3 PMID: 9500612
  18. The immunogenetics of human infectious diseases.
    Annu Rev Immunol. 1998;16:593-617 PMID: 9597143
  19. Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression.
    Nat Med. 1998 Jul;4(7):786-93 PMID: 9662369
  20. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS).
    Lancet. 1998 Sep 12;352(9131):866-70 PMID: 9742978
  21. Role of CCR2 genotype in the clinical course of syncytium-inducing (SI) or non-SI human immunodeficiency virus type 1 infection and in the time to conversion to SI virus variants.
    J Infect Dis. 1998 Dec;178(6):1806-11 PMID: 9815240
  22. Genetic acceleration of AIDS progression by a promoter variant of CCR5.
    Science. 1998 Dec 4;282(5395):1907-11 PMID: 9836644
  23. True HIV-1 infection in a pygmy.
    Lancet. 1987 Jun 27;1(8548):1499 PMID: 2885495
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.21.12004
Published
1999-10-12
Pages
12004-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18402
Subset
IM
Grants
NIAID NIH HHS · AI43279 · United States
NIAID NIH HHS · R37 AI046326 · United States
NIAID NIH HHS · R21 AI046326 · United States
NHLBI NIH HHS · R01 HL043521 · United States
NIAID NIH HHS · R01 AI043279 · United States
NIAID NIH HHS · R01 AI046326 · United States
NHLBI NIH HHS · HL43521 · United States
NIAID NIH HHS · AI46326 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.21.12004 PMC Full Text View journal details
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