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Concordance between the CC chemokine receptor 5 genetic determinants that alter risks of transmission and disease progression in children exposed perinatally to human immunodeficiency virus.

Abstract
If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial virus exposure are important determinants of virus entry and disease outcome, then the polymorphisms in CCR5 that influence risk of transmission and disease progression should be similar; this hypothesis was tested in a cohort of 649 Argentinean children exposed perinatally to human immunodeficiency virus type 1 (HIV-1). Two lines of evidence support this hypothesis. First, CCR5 haplotype pairs associated with enhanced risk of transmission were the chief predictors of a faster disease course. Second, some of the haplotype pairs associated with altered rates of transmission and disease progression in children were similar to those that we previously found influenced outcome in European American adults. This concordance suggests that CCR5 haplotypes may serve as genetic rheostats that influence events occurring shortly after initial virus exposure, dictating not only virus entry but, by extension, also the extent of early viral replication.
AuthorsA Mangano, E Gonzalez, R Dhanda, G Catano, M Bamshad, A Bock, R Duggirala, K Williams, S Mummidi, R A Clark, S S Ahuja, M J Dolan, R Bologna, L Sen, S K Ahuja
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 183 Issue 11 Pg. 1574-85 (Jun 01 2001) ISSN: 0022-1899 [Print] United States
PMID11335892 (Publication Type: 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.)
Chemical References
  • Receptors, CCR5
Topics
  • Acquired Immunodeficiency Syndrome (transmission)
  • Argentina
  • Cohort Studies
  • Disease Progression
  • Female
  • Genetic Variation
  • Genotype
  • HIV Infections (genetics, transmission, virology)
  • HIV-1
  • Haplotypes
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical
  • Pregnancy
  • Pregnancy Complications, Infectious (virology)
  • Receptors, CCR5 (genetics)

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