Chemokine receptor polymorphisms and human immunodeficiency virus disease progression.
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).
Easterbrook
P J
PJ
Dept. of HIV Medicine, Weston Education Centre, The Guy's, King's, London SE5 9RT, United Kingdom. philippa.easterbrook@kcl.ac.uk
Rostron
T
T
Ives
N
N
Troop
M
M
Gazzard
B G
BG
Rowland-Jones
S L
SL
D001727:Bisexuality; D016022:Case-Control Studies; D016001:Confidence Intervals; D017931:DNA Primers; D018450:Disease Progression; D005838:Genotype; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*; D013997:Time Factors
C515334:CCR2 protein, human; D017931:DNA Primers; D015483:HIV Antibodies; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine