The effect of CYP2C9 gene polymorphisms on blood pressure lowering response to losartan in patients with essential hypertension

Year 2022, Volume: 47 Issue: 3, 1015 - 1023, 30.09.2022

Funda Pepedil Tanrikulu , Melih O. Babaoglu , Banu Çakır , Atilla Bozkurt , Gülay Sain Güven

https://doi.org/10.17826/cumj.1093761

Abstract

Purpose: In this study, the possible effects of CYP2C9 polymorphisms on the clinical response to losartan were investigated in a group of hypertensive patients.
Materials and Methods: Seventy-four patients, newly diagnosed to have essential hypertension, and were subsequently prescribed losartan by attending physicians, were prospectively recruited for the study. Blood pressure measurements at the initiation of losartan treatment and six weeks after were completed for all participants. Genetic analysis for CYP2C9 polymorphisms was performed in blood samples collected at baseline. CYP2C9 *2 and *3 variant alleles were genotyped, and polymorphic patients' treatment responses were compared with the patients' who were carrying the wild type genotype.
Results: Analysis comparing the wild type genotype and CYP2C9*1*2 genotype revealed a trend toward more systolic blood pressure reduction in favor of wild-type genotype. However, there was no statistically significant difference between these two groups considering the change in diastolic blood pressure levels. Regarding the CYP2C9*1*3 genotype, there were no significant differences in systolic or diastolic blood pressure changes.
Conclusion: CYP2C9*1*2 polymorphism affects the systolic blood pressure response to losartan in hypertensive patients, while the CYP2C9*1*3 genotype was not shown in associated with systolic or diastolic blood pressure responses.
Keywords: Hypertension, losartan, CYP2C9, genetic polymorphism, pharmacogenetics

Keywords

Hypertension, losartan, CYP2C9, genetic polymorphism

CYP2C9 gen polimorfizmlerinin losartan kullanan hipertansif hastalarda tedavi yanıtı üzerine etkisi

Abstract

Amaç: Bu çalışmada, anti-hipertansif olarak losartan kullanan hastalarda CYP2C9 polimorfizmlerinin tedavi yanıtı üzerine etkileri incelenmiştir.
Yöntemler: Araştırmaya yeni tanı almış, evre 1 esansiyel hipertansiyonu olan 74 hasta dahil edildi. Bu hastalara tedavi öncesi ve losartan başlandıktan altı hafta sonra kan basıncı ölçümleri yapılarak elde edilen kan basıncı düşüşleri kaydedildi. Hastalardan ilk tanı sırasında alınmış olan kan örneklerinden DNA izolasyonu yapılarak CYP2C9 *2 ve *3 polimorfik alelleri için genetik analizler yapıldı. Polimorfik alelleri taşıyan bireyler ile yabanıl tip (wild-type) genotip taşıyıcılarının anti-hipertansif tedavi yanıtları karşılaştırıldı.
Bulgular: CYP2C9*1*2 genotipine sahip hastalar, yabanıl tip genotipe sahip hastalar ile kıyaslandığında diyastolik kan basıncı için gruplar arasında istatistiksel açıdan anlamlı fark saptanmazken, sistolik kan basıncındaki düşüşün yabanıl tip genotipe sahip hastalarda daha belirgin olma eğiliminde olduğu görüldü. CYP2C9*1*3 genotipi ise tedavi sonuçlarında anlamlı bir değişikliğe neden olmadı.
Sonuç: Bulgularımız, CYP2C9*1*2 polimorfizminin hipertansif hastaların losartan ile tedavisinde sistolik kan basıncı yanıtını etkileyebileceğini düşündürmektedir. Öte yandan, CYP2C9*1*3 genotipinin sistolik veya diyastolik kan basıncı yanıtlarıyla ilişkisi gösterilememiştir.
Anahtar kelimeler: Hipertansiyon, losartan, CYP2C9, genetik polimorfizm, farmakogenetik

Keywords

Genetik polimorfizm, Hipertansiyon, losartan, CYP2C9

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