Analysis of genetic polymorphisms in CCR5, CCR2, stromal cell-derived factor-1, RANTES, and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin in seronegative individuals repeatedly exposed to HIV-1.
To determine the influence of host genetics on human immunodeficiency virus (HIV) type 1 infection, we examined 94 repeatedly exposed seronegative (ES) individuals for polymorphisms in multiple genes and compared the results with those for 316 HIV-1-seropositive and 425 HIV-1-seronegative individuals. The frequency of homozygous C-C chemokine receptor (CCR) 5- Delta 32 was higher in ES (3.2%) than in HIV-1-seropositive individuals (0.0%; P=.012). However, the CCR5-59029A, CCR2-64I, stromal cell-derived factor (SDF)-1-3'A, RANTES (regulated on activation, normally T cell-expressed and -secreted)-403A, and RANTES-28G polymorphisms were not associated with resistance to HIV-1 infection. Furthermore, we identified novel variants in the DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin) repeat region and observed that heterozygous DC-SIGN reduced the risk of HIV-1 infection (3.2% in ES individuals vs. 0.0% in HIV-1-seropositive individuals; P=.011).
Department of Laboratory Medicine, University of Washington School of Medicine, 1959 N.E. Pacific Street, Seattle, WA 98195-8070, USA.
Huanliang
H
Liu
Yon
Y
Hwangbo
Sarah
S
Holte
Jean
J
Lee
Chunhui
C
Wang
Nicole
N
Kaupp
Haiying
H
Zhu
Connie
C
Celum
Lawrence
L
Corey
M Juliana
MJ
McElrath
Tuofu
T
Zhu
D000483:Alleles; D015815:Cell Adhesion Molecules / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics; D054377:Chemokine CXCL12; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC / Q000235:genetics; D015331:Cohort Studies; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D018023:HIV Seronegativity / Q000235:genetics*; D006679:HIV Seropositivity / Q000235:genetics; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics*; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D012307:Risk Factors; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D037181:Lectins, C-Type; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C515334:CCR2 protein, human; C515255:CXCL12 protein, human