Association between an interleukin-4 promoter polymorphism and the acquisition of CXCR4 using HIV-1 variants.
BACKGROUND
A polymorphism at position -589 in the interleukin 4 (IL-4) promoter region was recently described as being associated with the presence of syncytium-inducing CXCR4 using (X4) HIV-1 variants.


OBJECTIVE
To study the IL-4 promoter polymorphism -589T in relation to HIV-1 disease progression and acquisition of X4 HIV-1 variants.


METHODS
Retrospective longitudinal study among 342 HIV-1-infected homosexual men who participated in the Amsterdam Cohort study. Polymerase chain reaction was used in combination with restriction analysis to identify IL-4 promoter genotypes.


RESULTS
Carriers of the -589T allele (either -589 C/T heterozygotes or -589 T/T homozygotes), showed comparable progression to AIDS [relative hazard (RH), 0.94; P = 0.71], and survival (RH IL-4 -589 C/T or T/T, 0.94; P = 0.69) as carriers of the -589 C/C genotype (the reference group). In contrast to a previous study, we found that the -589T polymorphism was associated with a delayed acquisition of X4 HIV-1 variants (RH, 0.56; P = 0.02 for IL-4 -589 C/T or T/T) and a reduced number of CCR5 expressing memory CD4 T cells.


CONCLUSIONS
In the Amsterdam Cohort of homosexual men with HIV infection, the IL-4 -589T promoter polymorphism was associated with a delayed acquisition of X4 variants but did not affect overall disease progression.
Kwa
David
D
Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
van Rij
Ronald P
RP
Boeser-Nunnink
Brigitte
B
Vingerhoed
Jose
J
Schuitemaker
Hanneke
H
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D018451:Homosexuality, Male; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics*; D012189:Retrospective Studies
D019718:Receptors, CXCR4; D015847:Interleukin-4