Association between CACNA1C gene polymorphisms and ritodrine-induced adverse events in preterm labor patients

作者：Baek Min Young; Hwang Han Sung; Park Jin Young; Chung Jee Eun; Lee Kyung Eun; Lee Gwan Yung; Seong Jin Won; Yee Jeong; Kim Young Ju^*; Gwak Hye Sun^*

来源：European Journal of Clinical Pharmacology, 2017, 73(7): 837-842.

DOI：10.1007/s00228-017-2222-6

• Ritodrine
• CACNA1C
• Polymorphism
• Adverse drug events
• Preterm labor patients

Purpose 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 similar to 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.
Conclusion This study showed that CACNA1C gene polymorphisms could alter the probability of adverse drug event risk when ritodrine is used in preterm labor.

• 出版日期2017-7