Abstract
The present prospective follow-up study aimed to evaluate the effects of GRK5 polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in pregnant women undergoing preterm labor. A total of 162 women undergoing preterm labor were included in the study. Seven single nucleotide polymorphisms (SNPs) in the GRK5 gene (rs915120, rs2230345, rs2230349, rs7923896, rs1020672, rs4752308, and rs4752292) were assessed. Homozygous variant carriers of rs4752292 and rs1020672 had 0.6 times the hazard of delivery compared to wild-type allele carriers (95% confidence interval [CI], 0.41~0.99 and 0.38~0.99, respectively). In addition, homozygous variant carriers of rs4752292 and rs1020672 had 2.4-fold more (95% CI, 1.10~4.98) and 2.3-fold more (95% CI, 1.04~5.06) ADEs compared to those with the wild-type homozygotes, respectively. Among demographic variables, gestational age and modified Bishop score were significant factors associated with time to delivery, while body weight and maximum ritodrine infusion rate were significant factors associated with ADEs. In silico analysis showed that both rs4752292 and rs1020672 had the potential to affect mRNA splicing by alteration of splicing motifs. The present study shows that ritodrine efficacy and ADEs are associated with GRK5 gene polymorphisms in pregnant women undergoing preterm labor.
Highlights
The present prospective follow-up study aimed to evaluate the effects of GRK5 polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in pregnant women undergoing preterm labor
The pathogenesis of preterm labor and functional mechanism of tocolytics are yet to be fully understood, it has been reported that many tocolytics act via G-protein coupled receptor (GPCR) signal-mediated pathways involved in myometrium relaxation and contraction[2]
GPCR kinases are a class of protein kinases encoded by G protein-coupled www.nature.com/scientificreports receptor kinases (GRKs) genes, which are composed of the genes GRK1 to GRK7
Summary
The present prospective follow-up study aimed to evaluate the effects of GRK5 polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in pregnant women undergoing preterm labor. The present study shows that ritodrine efficacy and ADEs are associated with GRK5 gene polymorphisms in pregnant women undergoing preterm labor. The pathogenesis of preterm labor and functional mechanism of tocolytics are yet to be fully understood, it has been reported that many tocolytics act via G-protein coupled receptor (GPCR) signal-mediated pathways involved in myometrium relaxation and contraction[2]. Beta adrenergic receptors activated by catecholamines exhibit a key function in the mediation of uterine relaxation, as can be observed by the role of beta agonists such as ritodrine in preterm labor treatment[3,4]. Our previous study showed that ADRB2 polymorphisms affected beta agonist efficacy in pregnant women undergoing preterm labor[6]. Among the GRK4 family members, GRK4 is localized to the testis, while GRK5 and GRK6 display ubiquitous expression[8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
