Role of chemokine and cytokine polymorphisms in the progression of HIV-1 disease.
Allelic variants of the genes for chemokine receptors and their natural ligands, the chemokines, and cytokines can affect HIV-1 disease progression. This study investigates the level of expression of the CCR5-Delta32, CCR2b-641, RANTES In1.1C, SDF-1 3'A, IL-10-5'-592A and IL-4-589T alleles in two unique HIV-1 infected patient cohorts that represent the two distinct stages of disease progression, namely rapid progressors (RPs) and long term non-progressors (LTNPs) (n=12/group) were recruited. Quantitation of the gene expression of CCR5-Delta32, CCR2b-641, RANTES In1.1C, SDF-1 3'A, IL-10-5'-592A and IL-4-589T in peripheral blood mononuclear leukocytes (PBML) isolated from patients was performed by real time, quantitative (Q)-PCR using DNA was isolated from PBML. We observed that expression of these HIV-protective alleles was generally greater in the LTNP cohort than the RP cohort. LTNPs expressed more of the protective chemokine, SDF-1alpha than RPs, and no statistically significant difference was observed in RANTES production between the LTNPs and RPs. The LTNPs expressed significantly less amounts of cytokines IL-10 and IL-4 as compared to the RPs. Our results demonstrate that gene polymorphisms for CCR5-Delta32, CCR2b-641, RANTES In1.1C, SDF-1 3'A, IL-10-5'-592A and IL-4-589T may be used as clinical markers to predict progression of HIV-1 infections.
Mahajan
Supriya D
SD
Department of Medicine, Division of Allergy, State University of New York, Buffalo General Hospital, 100 High Street, Buffalo, NY 14203, USA. smahajan@buffalo.edu
Agosto-Mojica
Anardi
A
Aalinkeel
Ravikumar
R
Reynolds
Jessica L
JL
Nair
Bindukumar B
BB
Sykes
Donald E
DE
Martinez
Jeffery
J
Adams
Joshua
J
Singh
Neha
N
Bernstein
Zale
Z
Hsiao
Chiu-bin
CB
Schwartz
Stanley A
SA
D018925:Chemokines / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D018450:Disease Progression; D015870:Gene Expression; D005787:Gene Frequency; D005819:Genetic Markers; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D011110:Polymorphism, Genetic; D011379:Prognosis; D014176:Protein Biosynthesis
D018925:Chemokines; D016207:Cytokines; D005819:Genetic Markers