Spanish HIV-1-Infected Long-Term Nonprogressors of More... : JAIDS Journal of Acquired Immune Deficiency Syndromes (original) (raw)

Basic Science

Spanish HIV-1-Infected Long-Term Nonprogressors of More Than 15 Years Have an Increased Frequency of the CX3CR1 249I Variant Allele

Vidal, Francesc MD, PhD*; Viladés, Consuelo MD*; Domingo, Pere MD, PhD†; Broch, Montserrat PhD*; Pedrol, Enric MD, PhD‡; Dalmau, David MD, PhD§; Knobel, Hernando MD, PhD∥; Peraire, Joaquim MD*; Gutiérrez, Cristina PhD*; Sambeat, Ma Antònia MD, PhD†; Fontanet, Àngels†; Deig, Elisabeth MD‡; Cairó, Mireia MD§; Montero, Milagros MD∥; Richart, Cristóbal MD, PhD*; Mallal, Simon MD, PhD¶ on behalf of the Chemokines LTNP Study Group

From the *Hospital Universitari de Tarragona Joan XXIII and Universitat Rovira i Virgili, Tarragona, Catalonia, Spain; †Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, Spain; ‡Hospital General de Granollers, Spain; §Fundacio per a la Recerca. Hospital Mútua de Terrassa, Universitat de Barcelona, Spain; ∥Hospital del Mar de Barcelona, Spain; and ¶Royal Perth Hospital and Murdoch University, Perth, Western Australia.

See appendix for the Chemokines and LTNP Study Group members.

Received for publication April 14, 2005; accepted September 2, 2005.

Funded by The Marató de TV3 (02/1830, 02/1831, 02/1832, 02/1833, 02/1834); the Spanish AIDS Research Network (RIS G03/173); and the Fondo de Investigación Sanitaria (FIS 02/1282).

This work was presented in part at the 45th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Washington, DC; December 16-19, 2005; abstract no. ICAAC05-A-1860-ASM.

Reprints: Francesc Vidal, Department of Internal Medicine and Infectious Diseases, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili Mallafré Guasch, 4 43007 Tarragona, Catalonia, Spain (e-mail: [email protected]).

Abstract

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-1-infected Spanish patients.

Patients and 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 CCR5_Δ_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 χ2 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 CCR5_Δ_32.

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 CCR5_Δ_32 allele.