子痫前期中内皮糖蛋白途径的基因变异：挪威和拉丁裔队列的验证研究
Endoglin pathway genetic variation in preeclampsia: A validation study in Norwegian and Latina cohorts.
作者信息
Schmella Mandy J, Roberts James M, Conley Yvette P, Ren Dianxu, Storvold Gro L, Ingles Sue A, Wilson Melissa L, Staff Anne Catherine, Hubel Carl A
机构信息
Department of Health Promotion and Development (School of Nursing), University of Pittsburgh, Pittsburgh, PA, USA.
Department of Obstetrics, Gynecology, & Reproductive Sciences (School of Medicine), University of Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA; Department of Epidemiology (Graduate School of Public Health), University of Pittsburgh, Pittsburgh, PA, USA; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA; Global Pregnancy Collaboration, USA.
出版信息
Pregnancy Hypertens. 2018 Apr;12:144-149. doi: 10.1016/j.preghy.2017.10.005. Epub 2017 Nov 15.
OBJECTIVE
The purpose of this study was to validate our previous genetic association findings related to the endoglin (ENG) pathway from an American Caucasian preeclampsia cohort in independent preeclampsia cohorts. We also sought to explore the ENG pathway for new genetic associations in these independent cohorts.
STUDY DESIGN
We used a tagging single nucleotide (tSNP) approach to assess genetic variability across five ENG pathway genes (ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2) in a Caucasian cohort from Norway (n = 77 preeclampsia cases & n = 63 normotensive controls) and a White Hispanic cohort from Southern California (n = 69 preeclampsia cases & n = 106 normotensive controls).
MAIN OUTCOME MEASURES
Univariate analyses (Chi Square, Fisher's Exact) and multivariate logistic regression were conducted to evaluate the association between tSNP genotype distributions and pregnancy outcome in each cohort. Logistic regression models were adjusted for maternal age at delivery, infant sex, parity, smoking during pregnancy, and pre-pregnancy BMI.
RESULTS
Although we were unable to replicate our previous SNP-specific findings (ENG rs11792480, rs10121110; TGFβR2 rs6550005; p's > 0.05), we found that genetic variation in TGFβR1[ALK5] (rs6478974) and TGFβR2 (rs11129420, rs6802220, rs1155708, rs3773640, rs3773663) was significantly associated with preeclampsia in the Norwegian cohort and genetic variation in ALK1 (rs706819) and TGFβR2 (rs9843942) was significantly associated with preeclampsia in the Latina cohort.
CONCLUSION
Overall, our results provide further support for the involvement and investigation of the endoglin pathway in preeclampsia.
目的
本研究旨在验证我们之前在美国白人先兆子痫队列中有关内皮糖蛋白（ENG）通路的基因关联研究结果，并在独立的先兆子痫队列中进行验证。我们还试图在这些独立队列中探索ENG通路的新基因关联。
研究设计
我们采用标签单核苷酸（tSNP）方法，评估来自挪威的白种人队列（n = 77例先兆子痫病例和n = 63例血压正常对照）以及来自南加州的西班牙裔白人队列（n = 69例先兆子痫病例和n = 106例血压正常对照）中5个ENG通路基因（ENG、TGFβ1、TGFβR1、ALK1和TGFβR2）的遗传变异性。
主要观察指标
进行单因素分析（卡方检验、Fisher精确检验）和多因素逻辑回归，以评估每个队列中tSNP基因型分布与妊娠结局之间的关联。逻辑回归模型对分娩时的产妇年龄、婴儿性别、产次、孕期吸烟情况和孕前体重指数进行了校正。
结果
尽管我们未能重复之前的单核苷酸多态性（SNP）特异性研究结果（ENG rs11792480、rs10121110；TGFβR2 rs6550005；p值>0.05），但我们发现TGFβR1[ALK5]（rs6478974）和TGFβR2（rs11129420、rs6802220、rs1155708、rs3773640、rs3773663）的基因变异与挪威队列中的先兆子痫显著相关，而ALK1（rs706819）和TGFβR2（rs9843942）的基因变异与拉丁裔队列中的先兆子痫显著相关。
结论
总体而言，我们的结果为内皮糖蛋白通路参与先兆子痫并进行研究提供了进一步支持。
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