Koizumi Yusuke, Kageyama Seiji, Fujiyama Yoshihide, Miyashita Michiko, Lwembe Raphael, Ogino Keiki, Shioda Tatsuo, Ichimura Hiroshi
Department of Viral Infection and International Health, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
AIDS Res Hum Retroviruses. 2007 May;23(5):713-9. doi: 10.1089/aid.2006.0225.
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.
宿主免疫因子与HIV-1疾病进展之间的关系仍存在争议。与已发现可延缓HIV-1疾病进展的CCR5Delta32不同,仍有几个因素对临床病程的影响尚未得到证实。为了阐明这些关系,我们从先前报道的因素中选择了7个单核苷酸多态性(SNP),即RANTES启动子-28G/-403A、RANTES In1.1C、SDF-1 3'A、IL-4启动子-589T和DC-SIGN启动子-139C/-336C,并在日本感染HIV-1的血友病患者(n = 102)中进行了检测。通过直接测序法检测基因型,并比较两组之间的基因型分布和等位基因频率,这两组分别是静脉感染后10年以上未发展为艾滋病的缓慢进展者(n = 54)和其他患者(进展者)(n = 48)。RANTES -28G的等位基因频率在缓慢进展者(0.185)中显著高于进展者组(0.074)[p = 0.023,OR = 0.35,95%CI(0.142,0.880)]。DC-SIGN启动子-139C在进展者中的等位基因频率(0.333)显著高于缓慢进展者[0.204,p = 0.040,OR = 1.95,95%CI(1.039,3.677)]。对于RANTES -403A、RANTES In1.1C、SDF-1 3'A、IL-4 -589T和DC-SIGN -336C,两组之间的等位基因频率未观察到显著差异。这些结果表明,在感染HIV-1的日本血友病患者中,RANTES -28G与艾滋病进展延迟有关,而DC-SIGN -139C与艾滋病进展加速有关。