RANTES–28G Delays andDC-SIGN– 139C Enhances AIDS Progression in HIV Type 1-Infected Japanese Hemophiliacs

Abstract

The relationships between host immune factors and HIV-1 disease progression are still in dispute. Unlike CCR5Delta32, 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, and 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.

RANTES Gene Polymorphisms Associated with HIV-1 Infections in Kenyan Population

“…However, there is a clear trend towards slower rate of CD4 cell depletion in HIV-1-infected European Americans and Japanese [16]. However, reports have also shown protective effects of RANTES -28G on HIV disease progression in Thais [17] and delayed AIDS progression in HIV-1-infected Japanese haemophiliacs [18]. …”

Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population

“…Different studies have shown that polymorphisms in DC-SIGN and L-SIGN genes can influence susceptibility and/or resistance to HIV-1 [11][12][13]18,19].…”

“…DC-SIGN and L-SIGN genes polymorphisms have been involved in protection and susceptibility to infections, including HIV-1, in different ethnic groups [6,[11][12][13][14].…”

Association of RANTES −403 G/A, −28 C/G and In1.1 T/C polymorphism with HIV‐1 transmission and progression among North Indians

“…Although these results were not confirmed in subsequent studies in other ethnic groups in which the RANTES À28G frequency was lower than in the Japanese [Gonzalez et al, 2001;An et al, 2002;Zhao et al, 2004], McDermott et al reported that patients with RANTES À28G showed a clear trend towards slower rate of CD4 cell depletion in HIV-1 infected European Americans [McDermott et al, 2000]. Recent reports have shown the protective effect of RANTES À28G on HIV disease progression in Thais [Wichukchinda et al, 2006] while, delayed AIDS progression in HIV-1 infected Japanese hemophiliacs [Koizumi et al, 2007]. With respects to RANTES À403A variants, HIV-1 infected European American with RANTES À403A were initially reported to progress more slowly to AIDS [McDermott et al, 2000].…”

“…Recent studies of other populations reported that À403G allele may be associated with increased susceptibility to HIV infection [Zhao et al, 2004] whereas, no such association of RANTES À403 A/G and À28C/G polymorphism could be established in HIV-1 infected Ugandans [Cooke et al, 2006], North Indians [Suresh et al, 2006], and Spanish populations [Vidal et al, 2006]. In vitro functional data, acquired using luciferase reporter assays in transfected jurkat cells, demonstrated that the RANTES In1.1C allele was associated with reduced RANTES expression thus contributing to the rapid progression of AIDS in European-Americans and African-Americans [An et al, 2002], however, the SNP was not found to influence disease progression in Japanese Hemophiliacs [Koizumi et al, 2007]. RANTES In1.1 C without RANTES À28G had an accelerating effect on HIV disease progression [Wichukchinda et al, 2006].…”