RANTES-28G delays and DC-SIGN-139C enhances AIDS progression in HIV type 1-infected Japanese hemophiliacs

The relationships between host immune factors and HIV-1 disease progression are still in dispute. Unlike CCR5 Delta 32, which has been found to delay disease progression of HIV-1, there still remain several factors whose effect on the clinical course is unconfirmed. To clarify the relationships, we selected seven single-nucleotide polymorphisms (SNPs) out of the previously reported factors, namely, RANTES promoter -28G/-403A, RANTES In1.1C, SDF-1 3'A, IL-4 promoter -589T, and DC-SIGN promoter -139C/-336C, and examined these in Japanese HIV-1-infected hemophiliacs (n = 102). The genotypes were examined by the direct sequencing method, and the distributions of genotype and allelic frequencies were compared between two groups, slow progressors (n = 54) who did not develop AIDS more than 10 years after intravenous infection and others (progressors) (n = 48). The allelic frequency of RANTES -28G was significantly higher in slow progressors (0.185) than in the progressor group (0.074) [p = 0.023, OR = 0.35, 95% CI (0.142, 0.880)]. DC-SIGN promoter -139C appeared in progressors with significantly higher allelic frequency (0.333) than slow progressors [0.204, p = 0.040, OR = 1.95, 95% CI ( 1.039, 3.677)]. With RANTES -403A, RANTES In1.1C, SDF- 1 3' A, IL-4 -589T, and DC-SIGN -336C, no significant difference was observed in allelic frequencies between the two groups. These results suggest that RANTES -28G was associated with delayed AIDS progression, while DC- SIGN -139C was associated with accelerated AIDS progression in HIV-1-infected Japanese hemophiliacs.