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The role of polymorphisms in genes encoding chemokines and their receptors (CCR2B, SDF-1, and the promoter region of CCR5) in human immunodeficiency virus (HIV) disease progression was studied in 132 white HIV type 1 (HIV-1)-infected participants from a United Kingdom cohort study. Genotyping was done by use of amplification refractory mutation system-polymerase chain reaction with sequence-specific primers, and Cox proportional hazards models were used to examine the impact of polymorphisms on time to a CD4 cell count <200x106/L and to CDC stage IV disease. The results confirm a significant association of the CCR2B-64I mutant genotype with slower progression to a CD4 count <200 (hazards ratio [HR], 0.39; 95% confidence interval [CI], 0.17-0.91) but not with the SDF-1alpha 3' UTR homozygous mutation. The effects of the CCR5 and CCR2 mutations were genetically independent and similar in the magnitude of their protective effect on progression to a CD4 count <200 cells. A novel finding was an association of borderline significance between homozygosity for C at nucleotide position 59353 in the CCR5 promoter region and a slower rate of CD4 cell decline to <200x106/L (HR, 0. 58; 95% CI, 0.34-0.996).

Original publication

DOI

10.1086/314997

Type

Conference paper

Publication Date

10/1999

Volume

180

Pages

1096 - 1105

Keywords

Bisexuality, Case-Control Studies, Confidence Intervals, DNA Primers, Disease Progression, Genotype, HIV Antibodies, HIV Infections, HIV-1, Homosexuality, Male, Humans, Male, Point Mutation, Polymerase Chain Reaction, Polymorphism, Genetic, Prognosis, Promoter Regions, Genetic, Proportional Hazards Models, Receptors, CCR2, Receptors, CCR5, Receptors, Chemokine, Receptors, Cytokine, Time Factors