Spanish HIV-1-infected long-term nonprogressors of more than 15 years have an increased frequency of the CX3CR1 2491 variant allele

Background and Objectives: 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-infected Spanish patients. Patients and Methods: Two single-nucleotide polymorph isms, V2491 (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 CCR5 Delta 32 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 x(2) test and the Fisher exact test. Results: The frequencies of the 2491 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% Cl: 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 2491280T was significantly more common in LTNPs than in UPs (P = 0.0007). These results persisted after excluding from the analysis the individuals carrying the CCR5 Delta 32. Conclusions: CX3CR1 2491 variant allele is more frequent in Spanish HIV-1-infected LTNPs of > 15 years. This effect is independent of the presence of the CCR5 Delta 32 allele.