Publication Date:
1996-09-27
Description:
The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dean, M -- Carrington, M -- Winkler, C -- Huttley, G A -- Smith, M W -- Allikmets, R -- Goedert, J J -- Buchbinder, S P -- Vittinghoff, E -- Gomperts, E -- Donfield, S -- Vlahov, D -- Kaslow, R -- Saah, A -- Rinaldo, C -- Detels, R -- O'Brien, S J -- DA04334/DA/NIDA NIH HHS/ -- MO1-RR06020/RR/NCRR NIH HHS/ -- N01-HD-4-3200/HD/NICHD NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1996 Sep 27;273(5283):1856-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genomic Diversity, National Cancer Institute (NCI), Frederick, MD 21702-1201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8791590" target="_blank"〉PubMed〈/a〉
Keywords:
Acquired Immunodeficiency Syndrome/*genetics/immunology/physiopathology/virology
;
Base Sequence
;
Chromosome Mapping
;
Chromosomes, Human, Pair 3
;
Cohort Studies
;
Disease Progression
;
Genes
;
HIV Infections/*genetics/immunology/physiopathology/virology
;
*Hiv-1
;
Hemophilia A/complications
;
Heterozygote
;
Homosexuality, Male
;
Homozygote
;
Humans
;
Immunity, Innate/genetics
;
Male
;
Molecular Sequence Data
;
Receptors, CCR5
;
Receptors, Cytokine/*genetics
;
Receptors, HIV/*genetics
;
Risk Factors
;
*Sequence Deletion
;
Survival Analysis
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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