Effects of KCNMB2 gene polymorphisms on ritodrine therapy outcomes in women with preterm labor

Pharmacogenet Genomics. 2020 Aug;30(6):124-130. doi: 10.1097/FPC.0000000000000404.

Abstract

Objective: The present prospective follow-up study aimed to evaluate the effects of KCNMB2 gene polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in patients with preterm labor.

Methods: A total of 163 preterm labor patients were included in this single-center study. Nine single nucleotide polymorphisms (SNPs) in the KCNMB2 gene (rs10936979, rs7624046, rs7429015, rs7625907, rs6443559, rs9839376, rs9637454, rs11918114, and rs1382045) were assessed. The primary endpoint was time to delivery, and the secondary endpoint was ritodrine-induced ADEs.

Results: Patients with variant homozygotes of two SNPs (rs7624046 and rs9839376), which were in linkage disequilibrium, showed 2.06 [95% confidence interval (CI), 1.14-3.73] and 2.68 (95% CI, 1.16-6.20) times the hazard of time to delivery compared to wild-type allele carriers, respectively. Among demographic characteristics, gestational age at start of drug therapy and modified Bishop score were significant factors for time to delivery. Regarding safety outcomes, patients with variant homozygotes of rs7625907 had fewer ADEs compared to those with other genotypes (odds ratio, 0.32; 95% CI, 0.13-0.83).

Conclusion: This pharmacogenomic study suggests that ritodrine efficacy and ADEs are associated with KCNMB2 gene polymorphisms in patients with preterm labor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gestational Age
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channel beta Subunits / genetics*
  • Linkage Disequilibrium
  • Logistic Models
  • Maternal Age
  • Obstetric Labor, Premature / drug therapy*
  • Obstetric Labor, Premature / genetics
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Pregnancy Trimester, Second / genetics
  • Pregnancy Trimester, Third / genetics
  • Prospective Studies
  • Ritodrine / administration & dosage*
  • Ritodrine / adverse effects
  • Tocolytic Agents / administration & dosage*
  • Tocolytic Agents / adverse effects

Substances

  • KCNMB2 protein, human
  • Large-Conductance Calcium-Activated Potassium Channel beta Subunits
  • Tocolytic Agents
  • Ritodrine