Polymorphisms in the CCR5 Promoter Region Influence Disease Progression in Perinatally Human Immunodeficiency Virus Type 1–Infected Children

The effect of CC–chemokine receptor 5 (CCR5) promoter polymorphisms on the natural history of human immunodeficiency virus (HIV) disease was studied in 73 HIV-1–infected children. The CCR559338–59537 promoter haplotype, CCR5-59029A/G polymorphism, and CCR5Δ32 and CCR2-64I alterations were investigat...

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Bibliographic Details
Published in:The Journal of infectious diseases 2001-03, Vol.183 (5), p.814-818
Main Authors: Ometto, Lucia, Bertorelle, Roberta, Mainardi, Monica, Zanchetta, Marisa, Tognazzo, Sandro, Rampon, Osvalda, Ruga, Ezia, Chieco-Bianchi, Luigi, De Rossi, Anita
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age Factors
AIDS
Alleles
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
CCR5 protein
Child
Child, Preschool
Concise Communications
Disease Progression
Female
Genotypes
Haplotypes
HIV
HIV 1
HIV Infections - genetics
HIV Infections - transmission
Human immunodeficiency virus 1
Human viral diseases
Humans
Infant
Infant, Newborn
Infections
Infectious Disease Transmission, Vertical
Infectious diseases
Linkage Disequilibrium
Male
Medical genetics
Medical sciences
Oncology
Perinatal Care
Pharmacology. Drug treatments
Point Mutation
Polymorphism, Genetic
Promoter Regions, Genetic - genetics
Receptors, CCR5 - genetics
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
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Summary:The effect of CC–chemokine receptor 5 (CCR5) promoter polymorphisms on the natural history of human immunodeficiency virus (HIV) disease was studied in 73 HIV-1–infected children. The CCR559338–59537 promoter haplotype, CCR5-59029A/G polymorphism, and CCR5Δ32 and CCR2-64I alterations were investigated. After exclusion of carriers of CCR5Δ32 or CCR2-64I, Kaplan-Meier analysis disclosed that children with the P1/P159353C,59356C,59402A genotype progressed faster to disease than did children with other haplotypes (P=.016). When CCR2-64I carriers were included, this effect had borderline significance (P=.065) and was lost when CCR5Δ32 carriers were also considered (P=.387). The P1/P1 effect was strongest early after infection, when progression to disease was mainly associated with CCR5 coreceptor–using viruses. These results indicate that the P1/P1 genotype is predictive of rapid progression in HIV-1–infected children lacking CCR5Δ32 or CCR5-64I alleles. The observation of a linkage dis-equilibrium between P1 and 59029A might explain the previously reported association between 59029A homozygosity and rapid disease progression
ISSN:0022-1899
1537-6613
DOI:10.1086/318828