A common CD4 gene variant is associated with an increased risk of HIV-1 infection in Kenyan female commercial sex workers.
BACKGROUND
It has been predicted that CD4 C868T, a novel CD4 single-nucleotide polymorphism (SNP) that has been found to be highly prevalent among Africans, changes the tertiary structure of CD4, which may alter susceptibility to human immunodeficiency virus (HIV) infection.


METHODS
Participants were from a Kenyan cohort and included 87 uninfected and 277 HIV-1-infected individuals. DNA sequencing was used to determine CD4 genotype. A2.01 cells expressing similar levels of either wild-type CD4 or CD4-Trp240 as well as peripheral blood mononuclear cells from uninfected donors were infected with HIV-1(IIIB) or a Kenyan primary HIV-1 isolate. HIV-1 p24 enzyme-linked immunosorbent assay was used to determine the outcome of infection.


RESULTS
CD4 C868T was found to be significantly more prevalent among HIV-1-infected participants than among HIV-1-uninfected participants (P = .002), and C868T was associated with an increased incidence of HIV-1 infection as well (P = .005, log-rank test; P = .009, Wilcoxon test), with an odds ratio of 2.49 (P = .009). Both in vitro and ex vivo models demonstrated a significant association between CD4 C868T and susceptibility to HIV-1 infection (P < .001 and P = .003, respectively).


CONCLUSIONS
Overall, the present study found a strong correlation between CD4 C868T and increased susceptibility to HIV-1 infection. Given the high prevalence of both HIV infection and CD4 C868T in African populations, the effect of this SNP on the epidemic in Africa could be dramatic.
Oyugi
Julius O
JO
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Vouriot
Françoise C M
FC
Alimonti
Judie
J
Wayne
Stephen
S
Luo
Ma
M
Land
Allison M
AM
Ao
Zhujun
Z
Yao
Xiaojian
X
Sekaly
Rafick P
RP
Elliott
Lawrence J
LJ
Simonsen
J Neil
JN
Ball
T Blake
TB
Jaoko
Walter
W
Kimani
Joshua
J
Plummer
Francis A
FA
Fowke
Keith R
KR
D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology* / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics*; D003562:Cytidine / Q000235:genetics; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006720:Homozygote; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012189:Retrospective Studies; D011477:Sex Work; D013601:T-Lymphocytes / Q000276:immunology; D013936:Thymidine / Q000235:genetics; D014162:Transfection
D015704:CD4 Antigens; D017931:DNA Primers; D003562:Cytidine; D013936:Thymidine