The effect of genetic polymorphism of cytochrome P450 CYP2C9 on hypouremic effect of losartan

Hyperuricemia is associated with an increased risk of multiple diseases. Losartan may reduce serum uric acid levels. Genetic polymorphism of cytochrome P450 CYP2C9 that plays a key role in losartan metabolism may affect its pharmacokinetics and pharmacodynamics.

Aim

To study the hypouricemic effect of losartan in patients with grade I-II arterial hypertension depending on genetic polymorphism of cytochrome P450 CYP2C9.

Material and methods

Eighty seven patients (48 males; mean age 49.6 years) with grade I-II arterial hypertension were enrolled in the prospective study. Initially, we measured serum uric acid levels and performed genetic testing for allelic variants of the CYP2C9 gene (CYP2C9*2, CYP2C9*3) by PCR. Patients were distributed into two groups (CYP2C9*1/*1 genotype or homo- and heterozygous carriers of variant alleles CYP2C9*2 and CYP2C9*3) and were treated with losartan for 12 weeks. At the end of treatment, serum uric acid levels were measured again to evaluate the hypouricemic effect of losartan.

Results

CYP2C9 gene polymorphism had no effect on serum uric acid levels. At the end of 12-week treatment with losartan, median serum acid levels were 332 (275; 383) mcmol/L in carriers of CYP2C9*1/ *1 and 341 (271; 397) mcmol/L in patients with CYP2C9*2 or CYP2C9*3 (p = 0.869). In patients with hyperuricemia a statistically significant decrease in serum uric acid level from 414 (381; 500) to 397 (341; 452) mcmol/L (p = 0.005).

Conclusion

CYP2C9 gene polymorphism did not affect the serum uric acid concentration during losartan administration. The hypouricemic effect of losartan was found only in patients with baseline hyperuricemia.

Key words

Arterial hypertension, losartan, uric acid, hyperuricemia, CYP2C9, pharmacogenetics