The polymorphisms in DC-SIGNR affect susceptibility to HIV type 1 infection

• Published in: AIDS research and human retroviruses Vol. 23; no. 5; p. 686
• Main Authors: Wichukchinda, Nuanjun, Kitamura, Yoshihiro, Rojanawiwat, Archawin, Nakayama, Emi E, Song, Haihan, Pathipvanich, Panita, Auwanit, Wattana, Sawanpanyalert, Pathom, Iwamoto, Aikichi, Shioda, Tatsuo, Ariyoshi, Koya
• Format: Journal Article
• Language: English
• Published: United States 01.05.2007
• Subjects: Adult; Cell Adhesion Molecules - genetics; Cells, Cultured; Dendritic Cells; Female; Genetic Predisposition to Disease; Genotype; Haplotypes; HIV Infections - epidemiology; HIV Infections - genetics; HIV-1; Humans; Lectins, C-Type - genetics; Male; Polymorphism, Single Nucleotide; Receptors, Cell Surface - genetics; Reverse Transcriptase Polymerase Chain Reaction; Thailand - epidemiology; Thailand
• ISSN: 0889-2229
• DOI: 10.1089/aid.2006.0212

Dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN) and its homologue DC-SIGNR (DC-SIGN related) have been thought to play an important role in establishing HIV infection by enhancing trans-infection of CD4(+)T cells in the regional lymph nodes. To identify polymorphisms associated with HIV-exposed seronegative (ESN) individuals in Thais, genomic DNA from 102 HIV-seronegative individuals of HIV-seropositive spouses, 305 HIV-seropositive individuals, and 290 HIV-seronegative blood donors was genotyped for two single nucleotide polymorphisms (SNPs) in DC-SIGN promoter (-139A/G and 336A/G), a repeat number of 69 bp in Exon 4 of DC-SIGN and DC-SIGNR, and one SNP in Exon 5 of DC-SIGNR (rs2277998A/G). We found that the proportion of individuals possessing a heterozygous 7/5 and 9/5 repeat and A allele at rs2277998 of DC-SIGNR in HIV-seronegative individuals of HIV-seropositive spouses was significantly higher than HIV-seropositive individuals [p = 0.0373, OR (95% CI) = 0.57 (0.32,1.01); p = 0.0232, OR (95% CI) = 0.38 (0.15,0.98); and p = 0.0445, OR (95% CI) = 0.61 (0.37,1.02), respectively]. Analysis after stratifying by gender showed that these associations were observed only in females but not in males. Moreover, HIV-seropositive females tend to have a homozygous 7/7 repeat more frequently than HIV-seronegative females with a marginal level of significance [p = 0.0556, OR (95% CI) = 1.79 (0.94,3.40)]. Haplotype analysis showed that the proportion of individuals possessing the 5A haplotype in HIV-seronegative females was significantly higher than HIV-seropositive females [p = 0.0133, OR = 0.50 (0.27,0.90)]. These associations suggest that DC-SIGNR may affect susceptibility to HIV infection by a mechanism that is different in females and males. Further studies are warranted to investigate the mechanisms of their function.