Identifying genetic variants associated with ritodrine-induced pulmonary edema
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Lee, Seung Mi; Kim, So Yeon; Jung, Young Mi; Park, Chan-Wook; Park, Joong Shin] Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul, South Korea; [Park, Yoomi; Seo, Heewon; Min, Byung-Joo; Lee, Kye Hwa; Kim, Ju Han] Seoul Natl Univ, Div Biomed Informat, Coll Med, Seoul, South Korea; [Kim, Young Ju] Ewha Womans Univ, Dept Obstet & Gynecol, Coll Med, Seoul, South Korea; [Hwang, Han-Sung] Konkuk Univ, Dept Obstet & Gynecol, Sch Med, Seoul, South Korea; [Seo, Heewon] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada; [Lee, Suehyun] Konyang Univ, Dept Biomed Informat, Daejeon, South Korea; [Lee, Kye Hwa] Univ Ulsan, Asan Med Ctr, Dept Informat Med, Coll Med, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 PUBLIC LIBRARY SCIENCE
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000175091
- 본문언어 영어
- Published As http://dx.doi.org/10.1371/journal.pone.0241215
- PubMed https://pubmed.ncbi.nlm.nih.gov/33166306
초록/요약
Introduction Ritodrine is one of the most commonly used tocolytics in preterm labor, acting as a ss2-adrenergic agonist that reduces intracellular calcium levels and prevents myometrial activation. Ritodrine infusion can result in serious maternal complications, and pulmonary edema is a particular concern among these. The cause of pulmonary edema following ritodrine treatment is multifactorial; however, the contributing genetic factors remain poorly understood. This study investigates the genetic variants associated with ritodrine-induced pulmonary edema. Methods In this case-control study, 16 patients who developed pulmonary edema during ritodrine infusion [case], and 16 pregnant women who were treated with ritodrine and did not develop pulmonary edema [control] were included. The control pregnant women were selected after matching for plurality and gestational age at the time of tocolytic use. Maternal blood was collected during admission for tocolytic treatment, and whole exome sequencing was performed with the stored blood samples. Results Gene-wise variant burden (GVB) analysis resulted in a total of 71 candidate genes by comparing the cumulative effects of multiple coding variants for 19729 protein-coding genes between the patients with pulmonary edema and the matched controls. Subsequent data analysis selected only the statistically significant and deleterious variants compatible with ritodrine-induced pulmonary edema. Two final candidate variants in CPT2 and ADRA1A were confirmed by Sanger sequencing. Conclusions We identified new potential variants in genes that play a role in cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) regulation, which supports their putative involvement in the predisposition to ritodrine-induced pulmonary edema in pregnant women.
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