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SLCO1B1 Variants and Angiotensin Converting Enzyme Inhibitor (Enalapril)-Induced Cough: a Pharmacogenetic Study
Jian-Quan Luo1,2,3, Fa-Zhong He1,2,3, Zhen-Min Wang1,2,3
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; P. R. China.
Scientific Reports
|November 27, 2015
Summary
Genetic variations in SLCO1B1 significantly increase the risk of cough in patients taking enalapril, a common side effect of this angiotensin converting enzyme inhibitor. These findings identify potential pharmacogenetic markers for personalized enalapril treatment strategies.
Area of Science:
- Pharmacogenomics
- Cardiovascular Pharmacology
- Adverse Drug Reactions
Background:
- Cough is a frequent adverse effect of angiotensin converting enzyme inhibitors (ACEIs), particularly enalapril.
- Higher incidence of cough with ACEIs is observed in Chinese populations.
- Inter-individual variability in enalapril pharmacokinetics is influenced by SLCO1B1 genetic polymorphisms.
Purpose of the Study:
- To investigate the association between SLCO1B1 genetic polymorphisms and the risk of enalapril-induced cough.
- To identify potential pharmacogenetic markers for predicting enalapril-induced cough.
Main Methods:
- A cohort of 450 essential hypertension patients treated with enalapril was genotyped for SLCO1B1 variants (rs2306283 and rs4149056).
- Cough incidence was recorded as the primary endpoint in patients experiencing cough without an identifiable cause during enalapril treatment.
- Statistical analyses included relative risk calculation, haplotype analysis, and gene-dose effect assessment.
Main Results:
- The SLCO1B1 521C allele was associated with a 2-fold increased relative risk of enalapril-induced cough (P = 6.2 × 10(-4)).
- Carriers of the SLCO1B1*15/*15 haplotype showed a 6.94-fold increased risk of cough (P = 0.020).
- A significant gene-dose effect was observed, with cough incidence increasing from 28.2% to 71.4% with higher numbers of the 521C allele (trend P = 6.6 × 10(-4)).
Conclusions:
- SLCO1B1 genetic variants are strongly associated with an increased risk of enalapril-induced cough.
- These findings provide novel pharmacogenetic markers for enalapril treatment.
- Personalized medicine approaches may be enhanced by considering SLCO1B1 genotype in enalapril therapy.
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