CCR2b-64I Allelic Polymorphisms in Advanced HIV-Infected Koreans Accelerate Disease Progression

Abstract

Genetic polymorphisms of chemokine genes and chemokine-receptor genes in HIV-infected patients have been associated with delayed progression of this disease. The allelic frequencies of these genetic variants also differ between ethnic groups. To investigate the effects of the SDF1 and CCR2b genotypes on disease progression, survival of 200 HIV-infected persons for whom at least four subsequent immunologic data items had been collected was analyzed. A genotyping assay of SDF1 and CCR2b genes was carried out using polymerase chain reaction-restriction fragment length polymorphism analyses. HIV-infected persons heterozygous for the SDF1-3'A or CCR2b-64I alleles were included in the survival analysis, but homozygotes were excluded because of a very small sample number. Neither the CCR2b-+/64I allele nor the SDF1-+/3'A allele, separately or in combination, had a significant impact on survival during the asymptomatic period of HIV infection. However, CCR2b-+/64I alleles were associated with accelerated disease progression during the advanced period of HIV infection. The survival time of HIV-infected people with CCR2b-+/64I and SDF1-+/+ genotypes was significantly shorter than those of the other groups (p < 0.01), but this effect was not apparent in persons with CCR2b-+/64I alleles and SDF1-+/3'A genotypes. These results suggest that the effect of CCR2b-64I polymorphisms on disease progression may differ according to the stage of HIV infection and interactions with other gene variants.