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dc.contributor.authorKostrikis, Leondios G.
dc.contributor.authorNeumann, Avidan U.
dc.contributor.authorThomson, Bruce
dc.contributor.authorKorber, Bette T.
dc.contributor.authorMcHardy, Paul
dc.contributor.authorKaranicolas, Rose
dc.contributor.authorDeutsch, Lisa
dc.contributor.authorHuang, Yaoxing
dc.contributor.authorLew, Judy F.
dc.contributor.authorMcIntosh, Kenneth
dc.contributor.authorPollack, Henry
dc.contributor.authorBorkowsky, William
dc.contributor.authorSpeigel, Hans M.
dc.contributor.authorPalumbo, Paul
dc.contributor.authorOleske, James
dc.contributor.authorBardeguez, Arlene
dc.contributor.authorLuzuriaga, Katherine
dc.contributor.authorSullivan, John L.
dc.contributor.authorWolinsky, Steven M.
dc.contributor.authorKoup, Richard A.
dc.contributor.authorHo, David D.
dc.contributor.authorMoore, John P.
dc.date2022-08-11T08:10:12.000
dc.date.accessioned2022-08-23T16:58:51Z
dc.date.available2022-08-23T16:58:51Z
dc.date.issued1999-12-01
dc.date.submitted2012-05-01
dc.identifier.citationJ Virol. 1999 Dec;73(12):10264-71. <a href="http://jvi.asm.org/content/73/12/10264">Link to article on publisher's website</a>
dc.identifier.issn0022-538X (Linking)
dc.identifier.pmid10559343
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43457
dc.description.abstractThere are natural mutations in the coding and noncoding regions of the human immunodeficiency virus type 1 (HIV-1) CC-chemokine coreceptor 5 (CCR5) and in the related CCR2 protein (the CCR2-64I mutation). Individuals homozygous for the CCR5-Delta32 allele, which prevents CCR5 expression, strongly resist HIV-1 infection. Several genetic polymorphisms have been identified within the CCR5 5' regulatory region, some of which influence the rate of disease progression in adult AIDS study cohorts. We genotyped 1,442 infants (1,235 uninfected and 207 HIV-1 infected) for five CCR5 and CCR2 polymorphisms: CCR5-59353-T/C, CCR5-59356-C/T CCR5-59402-A/G, CCR5-Delta32, and CCR2-64I. The clinical significance of each genotype was assessed by measuring whether it influenced the rate of perinatal HIV-1 transmission among 667 AZT-untreated mother-infant pairs (554 uninfected and 113 HIV-1 infected). We found that the mutant CCR5-59356-T allele is relatively common in African-Americans (20.6% allele frequency among 552 infants) and rare in Caucasians and Hispanics (3.4 and 5.6% of 174 and 458 infants, respectively; P < 0.001). There were 38 infants homozygous for CCR5-59356-T, of whom 35 were African-Americans. Among the African-American infants in the AZT-untreated group, there was a highly significant increase in HIV-1 transmission to infants with two mutant CCR5-59356-T alleles (47.6% of 21), compared to those with no or one mutant allele (13.4 to 14.1% of 187 and 71, respectively; P < 0.001). The increased relative risk was 5.9 (95% confidence interval, 2.3 to 15.3; P < 0.001). The frequency of the CCR5-59356-T mutation varies between population groups in the United States, a low frequency occurring in Caucasians and a higher frequency occurring in African-Americans. Homozygosity for CCR5-59356-T is strongly associated with an increased rate of perinatal HIV-1 transmission.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10559343&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC113080/pdf/jv010264.pdf
dc.subject5' Untranslated Regions
dc.subjectAdult
dc.subject*African Americans
dc.subjectAlleles
dc.subjectAnti-HIV Agents
dc.subjectCohort Studies
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectGene Frequency
dc.subjectGenotype
dc.subjectHIV Infections
dc.subject*HIV-1
dc.subjectHispanic Americans
dc.subjectHumans
dc.subjectInfant
dc.subject*Infectious Disease Transmission, Vertical
dc.subjectLinkage Disequilibrium
dc.subjectPerinatal Care
dc.subject*Polymorphism, Genetic
dc.subjectReceptors, CCR2
dc.subjectReceptors, CCR5
dc.subject*Receptors, Chemokine
dc.subjectReceptors, Cytokine
dc.subjectRegulatory Sequences, Nucleic Acid
dc.subjectZidovudine
dc.subjectImmunology and Infectious Disease
dc.subjectPediatrics
dc.titleA polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants
dc.typeJournal Article
dc.source.journaltitleJournal of virology
dc.source.volume73
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_immunology/4
dc.identifier.contextkey2814334
html.description.abstract<p>There are natural mutations in the coding and noncoding regions of the human immunodeficiency virus type 1 (HIV-1) CC-chemokine coreceptor 5 (CCR5) and in the related CCR2 protein (the CCR2-64I mutation). Individuals homozygous for the CCR5-Delta32 allele, which prevents CCR5 expression, strongly resist HIV-1 infection. Several genetic polymorphisms have been identified within the CCR5 5' regulatory region, some of which influence the rate of disease progression in adult AIDS study cohorts. We genotyped 1,442 infants (1,235 uninfected and 207 HIV-1 infected) for five CCR5 and CCR2 polymorphisms: CCR5-59353-T/C, CCR5-59356-C/T CCR5-59402-A/G, CCR5-Delta32, and CCR2-64I. The clinical significance of each genotype was assessed by measuring whether it influenced the rate of perinatal HIV-1 transmission among 667 AZT-untreated mother-infant pairs (554 uninfected and 113 HIV-1 infected). We found that the mutant CCR5-59356-T allele is relatively common in African-Americans (20.6% allele frequency among 552 infants) and rare in Caucasians and Hispanics (3.4 and 5.6% of 174 and 458 infants, respectively; P < 0.001). There were 38 infants homozygous for CCR5-59356-T, of whom 35 were African-Americans. Among the African-American infants in the AZT-untreated group, there was a highly significant increase in HIV-1 transmission to infants with two mutant CCR5-59356-T alleles (47.6% of 21), compared to those with no or one mutant allele (13.4 to 14.1% of 187 and 71, respectively; P < 0.001). The increased relative risk was 5.9 (95% confidence interval, 2.3 to 15.3; P < 0.001). The frequency of the CCR5-59356-T mutation varies between population groups in the United States, a low frequency occurring in Caucasians and a higher frequency occurring in African-Americans. Homozygosity for CCR5-59356-T is strongly associated with an increased rate of perinatal HIV-1 transmission.</p>
dc.identifier.submissionpathpeds_immunology/4
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages10264-71


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