Stepanian Alain, Benchenni Soraya, Beillat-Lucas Tiphaine, Omnes Sophie, Defay Fannie, Peynaud-Debayle Edith, Baron Gabriel, Le Querrec Agnès, Dreyfus Michel, Salomon Laurence, Tsatsaris Vassilis, de Prost Dominique, Mandelbrot Laurent
AP-HP, Hôpital Louis Mourier, Service d'Hématologie Biologique, Colombes, France.
PLoS One. 2009 Jul 9;4(7):e6192. doi: 10.1371/journal.pone.0006192.
Preeclampsia and coronary-artery disease share risk factors, suggesting common pathophysiological mechanisms. CX3CR1/CX3CL1 mediates leukocyte migration and adhesion and has been implicated in the pathophysiology of several inflammatory diseases. M280/I249 variants of CX3CR1 are associated with an atheroprotective effect and reduced endothelial dysfunction. The aim of this study was to search for an association between V249I and T280M polymorphisms of CX3CR1, preeclampsia and endothelial dysfunction.
METHODOLOGY/PRINCIPAL FINDINGS: We explored these polymorphisms with real-time polymerase chain reaction in a case-control study (184 white women with preeclampsia and 184 matched normotensive pregnant women). Endothelial dysfunction biomarkers including von Willebrand factor, VCAM-1 and thrombomodulin, as well as the soluble form of CX3CL1 were measured by enzyme-linked immunosorbent assays (ELISA). The I249 and M280 alleles were associated neither with preeclampsia, nor with its more severe form or with endothelial injury. In contrast, we found a trend toward increased CX3CL1 levels in preeclampsia patients, especially in early-onset- preeclampsia as compared to its level in later-onset- preeclampsia.
CONCLUSIONS/SIGNIFICANCE: This is the first study to characterize the CX3CR1 gene polymorphisms in patients with preeclampsia. We found no differences in genotype or haplotype frequencies between patients with PE and normal pregnancies, suggesting that maternal CX3CR1 V249I and T280M polymorphisms do not increase susceptibility to preeclampsia. Further studies should be performed to directly evaluate the pathophysiological role of CX3CL1, a molecule abundantly expressed in endometrium, which has been shown to stimulate human trophoblast migration.
子痫前期和冠状动脉疾病具有共同的危险因素，提示存在共同的病理生理机制。CX3CR1/CX3CL1介导白细胞迁移和黏附，并与多种炎症性疾病的病理生理学相关。CX3CR1的M280/I249变异与动脉粥样硬化保护作用及内皮功能障碍减轻有关。本研究旨在探寻CX3CR1的V I249和T280M多态性、子痫前期与内皮功能障碍之间的关联。
方法/主要发现：在一项病例对照研究中（184例患子痫前期的白人女性和184例匹配的血压正常的孕妇），我们采用实时聚合酶链反应对这些多态性进行了探究。通过酶联免疫吸附测定（ELISA）法检测了包括血管性血友病因子、血管细胞黏附分子-1和血栓调节蛋白在内的内皮功能障碍生物标志物，以及CX3CL1的可溶性形式。I249和M280等位基因既与子痫前期无关，也与其更严重的形式或内皮损伤无关。相反，我们发现子痫前期患者，尤其是早发型子痫前期患者的CX3CL1水平有升高趋势，与晚发型子痫前期患者的CX3CL1水平相比有所升高。
结论/意义：这是第一项对子痫前期患者CX3CR1基因多态性进行特征描述的研究。我们发现子痫前期患者与正常妊娠者在基因型或单倍型频率上没有差异，这表明母体CX3CR1的V249I和T280M多态性不会增加患子痫前期的易感性。应开展进一步研究以直接评估CX3CL1的病理生理作用，CX3CL1是一种在内膜中大量表达的分子，已被证明可刺激人滋养细胞迁移。
