HIV Pathogenesis Programme, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
Optics & Imaging, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
Int J Mol Sci. 2024 Oct 9;25(19):10860. doi: 10.3390/ijms251910860.
Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms.
细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和 E-选择素是细胞黏附分子，在炎症中发挥重要作用，并与子痫前期的发病机制和 HIV 感染有关。更具体地说，在子痫前期中，ICAM-1、VCAM-1 和 E-选择素在细胞和合体滋养层细胞中的免疫表达失调，表明它们在胎盘功能不全中的作用。本研究调查了细胞间黏附分子-1（rs3093030）、血管细胞黏附分子-1（rs3783605）和 E-选择素（rs1805193）基因变异与非洲裔妇女子痫前期合并 HIV 感染的相关性。还研究了子痫前期发展的易感性和高效抗逆转录病毒治疗（HAART）的效果。共纳入 405 名妇女。其中 204 名为子痫前期，201 名为正常血压。临床特征包括母亲年龄、体重、血压（收缩压和舒张压）和孕龄。采集全血，提取 DNA，并对 ICAM-1（rs3093030 C>T）、VCAM-1（rs3783605 A>G）和 E-选择素（rs1805193 A>C）基因多态性进行基因分型。采用卡方检验进行比较。我们的结果表明，与子痫前期合并 HIV 感染的妇女相比，子痫前期妇女的分析变异频率更高。此外，ICAM-1（rs3093030 C>T）的 C 等位基因和 VCAM-1（rs3783605 A>G）的 G 等位基因在共病中发挥了更大的作用，可能被认为是非洲裔妇女子痫前期发展的危险因素。相反，E-选择素基因的 rs1805193 SNP 表明 A>C 仅与 HIV 感染显著相关，而与子痫前期无关。这些发现强调了 ICAM-1 基因的 rs3093030 SNP 和 VCAM-1 rs3783605 基因与子痫前期发展的强烈关联，表明它们在子痫前期中滋养细胞侵袭缺陷中的作用。亚组分析进一步表明，AA 基因型与晚发型子痫前期有关，这是一种疾病较轻的形式，表明早发型和晚发型之间存在不同的遗传易感性。
