title: Association between CACNA1C gene polymorphisms and ritodrine-induced adverse events in preterm labor patients.
abstract: OBJECTIVE
  As a tocolytic agent, ritodrine has been used in European and Asian countries but has lost popularity due to safety concerns. This study aimed to investigate the relationship between adverse drug events caused by ritodrine and the CACNA1C polymorphisms in preterm labor patients.
  
  
  METHODS
  Data were collected from medical records including maternal age, gestational age, body mass index, dilation score, effacement score, modified Bishop score, maximum infusion rate, and adverse drug events. Five single-nucleotide polymorphisms of the CACNA1C gene (rs10774053, rs215994, rs215976, rs2239128, and rs2041135) were analyzed.
  
  
  RESULTS
  One hundred eighty-six patients were included, 33 of whom had adverse drug events. A allele carriers of rs10774053 showed about 0.293-fold lower adverse drug events than GG genotype carriers (p = 0.012, absolute risk reduction = 16.5%) after adjusting for other confounding variables; the number needed to genotype for preventing one patient with GG genotype from suffering higher incidence of adverse drug events was calculated to be 14.6. Increase in maximum infusion rate of 1 mL/h was associated with a 1.03-fold (95% CI 1.01~1.06, p = 0.005) increased risk of adverse drug events. None of the patients with a CC genotype of rs215994 had adverse drug events, whereas 22.1% of the T allele carriers had adverse drug events.
  
  
  CONCLUSIONS
  This study showed that CACNA1C gene polymorphisms could alter the probability of adverse drug event risk when ritodrine is used in preterm labor.
authors.affiliation: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Baek
authors.affiliation: Department of Obstetrics and Gynecology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, 05030, Republic of Korea.
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon-si, Kyunggi-do, 16419, Republic of Korea.
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
authors.forename: Gwan Yung
authors.initials: GY
authors.lastname: Lee
authors.affiliation: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Seong
authors.affiliation: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Yee
authors.affiliation: Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, Seoul, 07985, Republic of Korea. kkyj@ewha.ac.kr.
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea. hsgwak@ewha.ac.kr.
authors.forename: Hye Sun
authors.identifier: http://orcid.org/0000-0003-0278-2563
authors.initials: HS
authors.lastname: Gwak
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D020746:Calcium Channels, L-Type / Q000235:genetics*; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D005838:Genotype; D006801:Humans; D007752:Obstetric Labor, Premature / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012312:Ritodrine / Q000009:adverse effects*; D015149:Tocolytic Agents / Q000009:adverse effects*; D014202:Tremor / Q000139:chemically induced
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D015149:Tocolytic Agents; D012312:Ritodrine
keywords: Adverse drug events; CACNA1C; Polymorphism; Preterm labor patients; Ritodrine