AEGiS-13IAC: Limited role of CCR5, CCR2 and SDF-1 polymorphisms in determining long-term nonprogressive course of HIV-1 infection.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Limited role of CCR5, CCR2 and SDF-1 polymorphisms in determining long-term nonprogressive course of HIV-1 infection.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrC371)

Balotta C, Mazzucchelli R, Corvasce S, Facchi G, Dehy L, Velleca R, Mazzucchelli R, Corvasce S, Facchi G, Dehy L, Velleca R, Saporetti G, Moroni M, Galli M, Saporetti G, Moroni M, Galli M
C. Balotta, University of Milan, Institute of Infectious and Tropical Diseases, 'L. Sacco' Hospital, via G. B. Grassi, 74, 20157 Milan, Italy, Tel.: +39 02 382 00 319, Fax: +39 02 356 66 44, E-mail: claudia.balotta@unimi.it

BACKGROUND: Conflicting data regarding the role of CCR5, CCR2 and SDF1 genes in delaying HIV-1 disease progression prompted us to study the prevalence of CCR5-D32, CCR2-64I and SDF1-3'A mutant alleles in Long-Term Nonprogressors (LTNPs) and subjects with a typical course of the disease (TPs).

METHODS: 77 LTNPs, 112 TPs and 117 healthy controls (HCs) were analyzed. CCR5, CCR2 and SDF-1 genotypes were detected by PCR, RG-PCR-RFLP and PCR-RFLP, respectively. Genetic data were correlated to CD4 cell counts and HIV-1 RNA in plasma.

RESULTS: CCR5 gene analysis revealed a lower frequency of D32 allele (.060) than the one found in Northern European countries (.137 in Swedish). LTNPs showed a significantly higher prevalence of CCR5-HE genotype (22.1%) compared to TPs (8.9%) (p = .030), whereas the proportion of CCR2-HE (15.6% vs 13.4%) and SDF1-HO (1.4% vs 8.1%) subjects was similar. A multivariate analysis performed in LTNPs considering age, CD4 counts, HIV-1 RNA levels and CCR5, CCR2 and SDF-1 polymorphisms, showed that individuals with SDF1-WT genotype had a lower risk of disease progression compared to SDF1-HE ones. The analysis performed considering both HE and HO genotypes as mutant condition showed that no protective combined genotypes were present in LTNPs compared to TPs. However, the CCR5-HE/CCR2-WT/SDF1-WT genotype was present in 14.3% LTNPs and 4.5% TPs (p = .02).

CONCLUSIONS: The frequency of CCR5-D32 allele is similar to that reported in Mediterranean countries confirming the presence of a North to South decreasing gradient of D32 allele across Eurasia. SDF1-WT status is associated with a low degree of viral activity in LTNPs. The analysis of combined genotypes did not identify a specific protective cluster of alleles in LTNPs. Taken together these results indicate a limited role of CCR5, CCR2 and SDF-1 alleles in establishing long-term nonprogressive condition.

Keywords: AEGIS, HIV Infections, Chemokines, CXC, HIV-1, Polymorphism (Genetics), Alleles, Disease Progression, Prevalence, Genotype, CD4 Lymphocyte Count, Polymorphism, Restriction Fragment Length, Polymerase Chain Reaction, CD4-CD8 Ratio, Europe, stromal cell-derived factor-1alpha, genetics, immunology
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TuOrC371