The polymorphisms in DC-SIGNR affect susceptibility to HIV type 1 infection.
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.
Wichukchinda
Nuanjun
N
National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand. nuanjun@health.moph.go.th
Kitamura
Yoshihiro
Y
Rojanawiwat
Archawin
A
Nakayama
Emi E
EE
Song
Haihan
H
Pathipvanich
Panita
P
Auwanit
Wattana
W
Sawanpanyalert
Pathom
P
Iwamoto
Aikichi
A
Shioda
Tatsuo
T
Ariyoshi
Koya
K
D000328:Adult; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002478:Cells, Cultured; D003713:Dendritic Cells; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000235:genetics*; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013785:Thailand / Q000453:epidemiology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human