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.
