Spanish HIV-1-infected long-term nonprogressors of more than 15 years have an increased frequency of the CX3CR1 249I variant allele.
OBJECTIVE
The influence of the polymorphisms of the CX3CR1 chemokine receptor gene on the natural history of HIV-1 infection is controversial. This study aimed to determine whether functionally active CX3CR1 genetic variants are associated with long-term nonprogressive infection of >15 years in HIV-1-infected Spanish patients.


METHODS
Two single-nucleotide polymorphisms, V249I (G > A) and T280M (C > T), of the CX3CR1 gene were assessed in 271 Spaniards. These included 60 HIV-1-infected patients who were long-term nonprogressors (LTNPs) of >15 years, 109 HIV-1-infected patients who were usual progressors (UPs), and 102 control subjects. The CCR5Delta32 was also assessed. Genotyping was performed using polymerase chain reaction and automatic sequencing analysis methods on white cell DNA. Genotype and allele frequencies were compared by the chi test and the Fisher exact test.


RESULTS
The frequencies of the 249I variant allele were 42% for LTNPs, 24.5% for UPs, and 35% for healthy controls; the differences between LTNPs and UPs were significant (odds ratio 0.46; 95% CI: 0.27 to 0.75; P = 0.0017). For 280M the distribution was 16% for LTNPs, 14% for UPs, and 17% for healthy controls (P = NS). The haplotype 249I280T was significantly more common in LTNPs than in UPs (P = 0.0007). These results persisted after excluding from the analysis the individuals carrying the CCR5Delta32.


CONCLUSIONS
CX3CR1 249I variant allele is more frequent in Spanish HIV-1-infected LTNPs of >15 years. This effect is independent of the presence of the CCR5Delta32 allele.
Vidal
Francesc
F
Hospital Universitari de Tarragona Joan XXIII and Universitat Rovira i Virgili, Tarragona, Catalonia, Spain. fvidal@comt.es
Viladés
Consuelo
C
Domingo
Pere
P
Broch
Montserrat
M
Pedrol
Enric
E
Dalmau
David
D
Knobel
Hernando
H
Peraire
Joaquim
J
Gutiérrez
Cristina
C
Sambeat
Ma Antònia
MA
Fontanet
Angels
A
Deig
Elisabeth
E
Cairó
Mireia
M
Montero
Milagros
M
Richart
Cristóbal
C
Mallal
Simon
S
D000328:Adult; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics*; D020276:HIV Long-Term Survivors; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000235:genetics*; D013030:Spain / Q000453:epidemiology
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D008565:Membrane Proteins; D019707:Receptors, Chemokine