Leonardo Daniela P, Albuquerque Dulcinéia M, Lanaro Carolina, Baptista Letícia C, Cecatti José G, Surita Fernanda G, Parpinelli Mary A, Costa Fernando F, Franco-Penteado Carla F, Fertrin Kleber Y, Costa Maria Laura
Hematology and Hemotherapy Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Department of Obstetrics and Gynaecology, School of Medicine, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
PLoS One. 2015 Aug 28;10(8):e0136693. doi: 10.1371/journal.pone.0136693. eCollection 2015.
Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations.
To investigate the association of single nucleotide polymorphisms (SNPs) in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4), MMP2 (C-1306T), and MMP9 (C-1562T) genes with preeclampsia in patients from Southeastern Brazil.
This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome.
We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women.
Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications.
子痫前期是全球孕产妇和新生儿发病及死亡的主要原因之一，但其发病仍然不可预测，病理生理学也尚未完全阐明。基因研究已将编码一氧化氮合酶和基质金属蛋白酶的基因中的单核苷酸多态性与子痫前期相关联，但不同人群的研究结果大多尚无定论。
研究巴西东南部患者中一氧化氮合酶3（NOS3）基因（G894T、T-786C以及内含子4中的可变数目串联重复序列VNTR）、基质金属蛋白酶2（MMP2）基因（C-1306T）和基质金属蛋白酶9（MMP9）基因（C-1562T）的单核苷酸多态性与子痫前期的关联。
这项前瞻性病例对照研究纳入了77例子痫前期患者和266例对照孕妇。收集临床数据以评估危险因素以及子痫和HELLP（溶血、肝酶升高和血小板减少）综合征等严重并发症的情况。
我们发现单核苷酸多态性NOS3 T-786C与子痫前期之间存在显著关联，独立于年龄、身高、体重或所研究的其他单核苷酸多态性，且未发现与其他多态性存在关联。年龄和子痫前期病史也被确定为危险因素。NOS3 T-786C至少存在一个多态性等位基因也与子痫前期患者中子痫或HELLP综合征的发生相关。
我们的数据支持NOS3 T-786C单核苷酸多态性与子痫前期及其并发症的严重程度相关。
