Association of CYP2C9 and SLCO1B1 genetic variants with an effective dose of torasemide in patients with chronic heart failure

Gafurova N.M.: Sechenov First Moscow State Medical University, Moscow

Kazakov R.E.: Scientific Centre for Expert Evaluation of Medicinal Products

Murashko S.S.: Clinical Hospital of the Presidential Administration of Russia, Moscow, Russia

Shikh E.V.: Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov First Moscow State Medical University, Moscow

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Summary

Aim

To study the association of gene polymorphism CYP2С9*2 (rs1799853, c.430C>T, Arg144Cys), CYP2C9*3 (rs1057910, 1075A>C, Ile359Leu) and SLCO1B1*5 (rs4149056, c.521T>C, Val174Ala) with an effective dose of torasemide in patients with chronic heart failure (HF).

Material and methods

The study included 50 patients (31 men and 19 women; median age 76) with NYHA class I-IV taking torasemide. Real-time PCR was used to determine allelic variants of the CYP2C9 and SLCO1B1 genes.

Results

The genotypes of the studied patients with HF were distributed as follows: 38 (76%) had the CYP2C9*1/*1 genotype, 7 (14%) had the CYP2C9*1/*2 genotype, 4 (8%) had the CYP2C9*1/*3 genotype, 1 (2%) had the CYP2C9*2/*2 genotype The c.521T>C distribution of the SLCO1B1 gene was as follows: 32 (64%) had the c.521TT genotype, 14 (28%) had the c.521TC genotype, and 4 (8%) had the c.521CC genotype. The allele and genotype frequencies of CYP2C9*2 (χ2 = 1.06, p = 0.91), CYP2C9*3 (χ2 = 0.8, p = 0.96) and c.521C of the SLCO1B1 gene (χ2 = 1.7, p = 0.78) were consistent with the Hardy–Weinberg equilibrium. The optimal effective dose of torasemide was 2.5 mg in 8 (16%) patients, 5 mg in 27 (54%) patients and 10 mg in 15 (30%) patients. There was no statistically significant relationship between the effective dose of torasemide and the CYP2С9 and SLCO1B1 genotypes in patients with HF (p=0.673 and p=0.207, respectively).

Conclusion

Carriage of the allelic variants CYP2С9*2 (rs1799853), CYP2C9*3 (rs1057910) of the CYP2C9 gene and c.521C (rs4149056) of the SLCO1B1 gene was not associated with the effective dose of torasemide in patients with HF.

Key words

Heart failure, loop diuretics, torasemide, pharmacogenetics, gene polymorphism, CYP2C9, SLCO1B1.