Effect of genetic variants of CCR2 and CCL2 on the natural history of HIV-1 infection: CCL2-2518GG is overrepresented in a cohort of Spanish HIV-1-infected subjects.
OBJECTIVE
Polymorphisms in the genes that encode for the CCR2 chemokine receptor and its natural ligand CCL2 have been shown to influence the natural history of HIV-1 infection, although data are inconsistent. Our aim was to determine whether functionally active CCR2 and CCL2 genetic variants influence the risk of infection and disease progression in a cohort of white Spaniards.


METHODS
This was a multicenter genetic association case-control study. Two single nucleotide polymorphisms (SNPs), V64I (G > A) of the CCR2 gene and -2518 (A > G) of the CCL2 gene, were assessed in 318 individuals: 73 HIV-1-infected long-term nonprogressors (LTNPs) of >16 years duration, 109 HIV-1-infected usual progressors (UPs), 36 heavily exposed to HIV-1 but uninfected individuals (EUs), and 100 control subjects. The distribution of the CCR5Delta32 allele was also assessed. Genotyping was performed using polymerase chain reaction (PCR) restriction fragment length polymorphisms (RFLPs) or PCR and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared by the chi2 test and the Fisher exact test.


RESULTS
CCR2 genotype distribution and allele frequencies showed nonsignificant differences between groups. The distribution of CCL2 alleles showed no significant differences between groups. HIV-1-infected individuals had, however, a significantly higher prevalence of the variant homozygous CCL2 GG genotype compared with EUs (P = 0.02). This result persisted when we studied only individuals with wild-type CCR5. Genotype and allele distribution of CCL2 was similar in HIV-1-infected UPs and LTNPs.


CONCLUSIONS
In our cohort of white Spaniards, homozygosity for the variant CCL2-2518GG genotype is overrepresented in HIV-1-infected subjects.
Viladés
Consuelo
C
Department of Internal Medicine, Infectious Diseases and AIDS Research unit, Hospital Universitari de Tarragona Joan XXIII and Universitat Rovira i Virgili, Tarragona, Spain.
Broch
Montserrat
M
Plana
Montserrat
M
Domingo
Pere
P
Alonso-Villaverde
Carlos
C
Pedrol
Enric
E
Knobel
Hernando
H
Dalmau
David
D
Peraire
Joaquim
J
Gutiérrez
Cristina
C
López
Anna
A
Sambeat
Maria Antònia
MA
Olona
Montserrat
M
Garcia
Felipe
F
Richart
Cristóbal
C
Gatell
Josep Maria
JM
Vidal
Francesc
F
D000328:Adult; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D015497:HIV-1; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013030:Spain
C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine