Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)
Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.
Winkler
C
C
Science Applications International Corporation (SAIC), National Cancer Institute, Frederick, MD 21702, USA.
Modi
W
W
Smith
M W
MW
Nelson
G W
GW
Wu
X
X
Carrington
M
M
Dean
M
M
Honjo
T
T
Tashiro
K
K
Yabe
D
D
Buchbinder
S
S
Vittinghoff
E
E
Goedert
J J
JJ
O'Brien
T R
TR
Jacobson
L P
LP
Detels
R
R
Donfield
S
S
Willoughby
A
A
Gomperts
E
E
Vlahov
D
D
Phair
J
J
O'Brien
S J
SJ
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology; D000328:Adult; D054377:Chemokine CXCL12; D018925:Chemokines / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D019743:Chemokines, CXC; D015331:Cohort Studies; D018450:Disease Progression; D005796:Genes; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D044469:Racial Groups; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000821:virology
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine