TY - JOUR

T1 - Targeted sequencing analysis of ACVR2A gene identifies novel risk variants associated with preeclampsia

AU - Glotov, Andrey S

AU - Kazakov, Sergey V

AU - Vashukova, Elena S

AU - Pakin, Vladimir S

AU - Danilova, Maria M

AU - Nasykhova, Yulia A

AU - Masharsky, Aleksey E

AU - Mozgovaya, Elena V

AU - Eremeeva, Dina R

AU - Zainullina, Marina S

AU - Baranov, Vladislav S

PY - 2018/3/19

Y1 - 2018/3/19

N2 - BACKGROUND: Preeclampsia (PE) is the most common complication of pregnancy that remains to be a major cause of maternal and fetal mortality. Prediction and early diagnosis of PE would allow for timely initiation of preventive therapy. According to recent studies of ACVR2A gene polymorphism is associated with PE, but it is still unclear whether these findings reflect specific pathogenetic mechanisms of this disease.METHODS: We performed targeted next-generation sequencing (NGS) sequencing of ACVR2A gene by means of Ion Torrent Personal Genome machine (PGM) Sequencer. A genetic analysis of patients with PE and control group was performed. Bioinformatics analysis using Polyphen2 (Boston, MA), SIFT (La Jolla, CA), and SnpSift software were used. To select genetic markers in PE patients two additive models and score analysis were applied.RESULTS: Based on the score analysis, we detected two substitutions (rs145399059 and rs17692648) and one insertion insAA at position 148642724 that were associated with PE in our cohorts. We also detected a variant rs17742573 that can be considered as protective against preeclampsia.CONCLUSIONS: Our data suggest that some variants in ACVR2A gene are associated with PE. But more studies are required to reveal the role of ACVR2A gene in the pathogenesis of this disease during pregnancy.

AB - BACKGROUND: Preeclampsia (PE) is the most common complication of pregnancy that remains to be a major cause of maternal and fetal mortality. Prediction and early diagnosis of PE would allow for timely initiation of preventive therapy. According to recent studies of ACVR2A gene polymorphism is associated with PE, but it is still unclear whether these findings reflect specific pathogenetic mechanisms of this disease.METHODS: We performed targeted next-generation sequencing (NGS) sequencing of ACVR2A gene by means of Ion Torrent Personal Genome machine (PGM) Sequencer. A genetic analysis of patients with PE and control group was performed. Bioinformatics analysis using Polyphen2 (Boston, MA), SIFT (La Jolla, CA), and SnpSift software were used. To select genetic markers in PE patients two additive models and score analysis were applied.RESULTS: Based on the score analysis, we detected two substitutions (rs145399059 and rs17692648) and one insertion insAA at position 148642724 that were associated with PE in our cohorts. We also detected a variant rs17742573 that can be considered as protective against preeclampsia.CONCLUSIONS: Our data suggest that some variants in ACVR2A gene are associated with PE. But more studies are required to reveal the role of ACVR2A gene in the pathogenesis of this disease during pregnancy.

KW - ACVR2A

KW - NGS

KW - Polymorphism

KW - SNP

KW - mutations

KW - pre-eclampsia

KW - pregnancy

UR - http://www.scopus.com/inward/record.url?scp=85044342475&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/targeted-sequencing-analysis-acvr2a-gene-identifies-novel-risk-variants-associated-preeclampsia

U2 - 10.1080/14767058.2018.1449204

DO - 10.1080/14767058.2018.1449204

M3 - Article

C2 - 29506428

SP - 1

EP - 7

JO - Journal of Maternal-Fetal and Neonatal Medicine

JF - Journal of Maternal-Fetal and Neonatal Medicine

SN - 1476-7058

ER -