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

• Published in: The Journal of infectious diseases Vol. 183; no. 5; pp. 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: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.03.2001; University of Chicago Press; Oxford University Press
• 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; Human; Immunopathology; HIV-1 virus; Retroviridae; CCR2 chemokine receptor; AIDS; Chemokine receptor; CC chemokine; Lentivirus; Immune deficiency; Infection; Virus; CCR5 chemokine receptor; Allele; Viral disease; Human immunodeficiency virus; Child; Haplotype; CC chemokine receptor; Polymorphism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/318828

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