Laboratório de Imunobiologia e Imunogenética, Programa de Pós-Graduação em Genética e Biologia Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
Departamento de Farmacologia, Instituto de Biociências, UNESP-Universidade Estadual Paulista, Botucatu, SP, Brazil.
Int J Immunogenet. 2019 Apr;46(2):82-87. doi: 10.1111/iji.12416. Epub 2019 Feb 20.
Pre-eclampsia (PE) is a hypertensive disorder that affects an important number of pregnant women worldwide. The exact causes of PE remain poorly understood. However, inflammation and deregulation of innate immune cells, such as natural killer (NK) cells, contribute to PE pathogenesis. Besides, the mother's genetic background also impacts on PE susceptibility. Thus, genetic variants that potentially modify the behaviour of inflammatory cells may help us to understand the causes of PE. Variants of genes encoding NKG2C (expressed in NK cells) and C-C chemokine receptor type 5 (CCR5) (expressed mainly in leucocytes) are important targets in the study of gestational disorders. In this context, we evaluated the impact of both NKGC2 gene deletion and CCR5Δ32 gene variant on PE susceptibility in a population sample from central-southeast Brazil composed by 369 women (156 with PE and 213 healthy pregnant women). No statistically significant association between the NKG2C gene deletion and susceptibility to PE was observed. However, taking into consideration the important role of NK cells in pregnancy, the influence of NKG2C gene deletion on PE pathogenesis should not be ruled out and deserves further studies in populations with different genetic/ethnic backgrounds. In addition, our results regarding CCR5Δ32 corroborate previous data from our group approaching a distinct cohort and reinforce CCR5Δ32 as a protective factor against PE development (p < 0.05).
子痫前期 (PE) 是一种影响全球大量孕妇的高血压疾病。PE 的确切病因仍不清楚。然而，炎症和先天免疫细胞（如自然杀伤 (NK) 细胞）的失调导致了 PE 的发病机制。此外，母亲的遗传背景也会影响 PE 的易感性。因此，潜在改变炎症细胞行为的遗传变异可能有助于我们了解 PE 的病因。编码 NKG2C（在 NK 细胞中表达）和 C-C 趋化因子受体 5（CCR5）（主要在白细胞中表达）的基因变异是妊娠障碍研究中的重要靶点。在这方面，我们评估了 NKG2C 基因缺失和 CCR5Δ32 基因变异对来自巴西中东南部的一个人群样本（369 名女性，其中 156 名患有 PE，213 名健康孕妇）中 PE 易感性的影响。未观察到 NKG2C 基因缺失与 PE 易感性之间存在统计学显著关联。然而，考虑到 NK 细胞在妊娠中的重要作用，不应排除 NKG2C 基因缺失对 PE 发病机制的影响，并且值得在具有不同遗传/种族背景的人群中进一步研究。此外，我们关于 CCR5Δ32 的结果与我们小组以前的数据相吻合，该数据涉及到不同的队列，并且加强了 CCR5Δ32 作为 PE 发展的保护因素（p<0.05）。
