Wichukchinda Nuanjun, Kitamura Yoshihiro, Rojanawiwat Archawin, Nakayama Emi E, Song Haihan, Pathipvanich Panita, Auwanit Wattana, Sawanpanyalert Pathom, Iwamoto Aikichi, Shioda Tatsuo, Ariyoshi Koya
National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
AIDS Res Hum Retroviruses. 2007 May;23(5):686-92. 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.
树突状细胞特异性细胞间黏附分子-3（ICAM-3）抓取非整合素（DC-SIGN）及其同源物DC-SIGNR（DC-SIGN相关分子），被认为通过增强区域淋巴结中CD4(+)T细胞的转染感染，在建立HIV感染过程中发挥重要作用。为了鉴定泰国人群中与HIV暴露血清阴性（ESN）个体相关的多态性，对102名HIV血清阳性配偶的HIV血清阴性个体、305名HIV血清阳性个体和290名HIV血清阴性献血者的基因组DNA进行基因分型，检测DC-SIGN启动子中的两个单核苷酸多态性（SNP）（-139A/G和336A/G）、DC-SIGN和DC-SIGNR外显子4中69 bp的重复次数，以及DC-SIGNR外显子5中的一个SNP（rs2277998A/G）。我们发现，在HIV血清阳性配偶的HIV血清阴性个体中，DC-SIGNR的rs2277998位点具有杂合7/5和9/5重复以及A等位基因的个体比例显著高于HIV血清阳性个体 [p = 0.0373，OR（95% CI）= 0.57（0.32,1.01）；p = 0.0232，OR（95% CI）= 0.38（0.15,0.98）；p = 0.0445，OR（95% CI）= 0.61（0.37,1.02），分别]。按性别分层后的分析表明，这些关联仅在女性中观察到，而在男性中未观察到。此外，HIV血清阳性女性比HIV血清阴性女性更频繁地出现纯合7/7重复，具有边缘显著性水平 [p = 0.0556，OR（95% CI）= 1.79（0.94,3.40）]。单倍型分析表明，HIV血清阴性女性中具有5A单倍型的个体比例显著高于HIV血清阳性女性 [p = 0.0133，OR = 0.50（0.27,0.90）]。这些关联表明，DC-SIGNR可能通过一种在女性和男性中不同的机制影响HIV感染的易感性。有必要进一步研究其功能机制。
