CYP2C9 gene polymorphisms influence on antihypertensive effectiveness and hypouricemic effect of losartan among patients with arterial hypertension : an observational study
© 2022 Walter de Gruyter GmbH, Berlin/Boston..
OBJECTIVES: CYP2C9 gene polymorphic variants can decrease the effects of losartan, reducing active metabolite (E-3174) formation. Study aims to determine the influence of *2 (+430C>T; rs799853) and *3 (+1075A>C; rs1057910) CYP2C9 gene polymorphic variants on the hypotensive and uricosuric effect of losartan on patients with arterial hypertension.
METHODS: Eighty one patients with stage 1-2 arterial hypertension newly diagnosed with ABMP were enrolled in the study. Physicians started losartan treatment and then we measured urine concentration of E-3174/losartan to estimate CYP2C9 activity. After 3-month losartan treatment we compared effectiveness of the therapy with ABPM and plasma uric acid level between carriers of CYP2C9 *1/*1 and CYP2C9 gene polymorphic variants (*2 and *3).
RESULTS: Carriage of CYP2C9*2 and CYP2C9*3 alleles reduced the hypotensive effect of losartan (p<0.001, OR=8.13 (95% CI, 2.75-23.97)). Analysis of the ABPM data revealed that blood pressure was significantly higher in patients with polymorphic genotypes. There was no significant difference in uric acid level in plasma and losartan and its metabolite concentration in urine between genotypes.
CONCLUSIONS: Carriage of low function polymorphic variants of the CYP2C9 gene (*2 and *3) reduced the hypotensive effect of losartan according to ABPM and don't affect uric acid level in plasma and E-3174/losartan in urine.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
|---|---|
| Enthalten in: |
Drug metabolism and personalized therapy - 38(2023), 2 vom: 01. Juni, Seite 163-168 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sinitsina, Irina I [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.06.2023 Date Revised 14.06.2023 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1515/dmpt-2022-0115 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM350917981 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM350917981 | ||
| 003 | DE-627 | ||
| 005 | 20231226050103.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1515/dmpt-2022-0115 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1169.xml |
| 035 | |a (DE-627)NLM350917981 | ||
| 035 | |a (NLM)36580432 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sinitsina, Irina I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CYP2C9 gene polymorphisms influence on antihypertensive effectiveness and hypouricemic effect of losartan among patients with arterial hypertension |b an observational study |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.06.2023 | ||
| 500 | |a Date Revised 14.06.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 Walter de Gruyter GmbH, Berlin/Boston. | ||
| 520 | |a OBJECTIVES: CYP2C9 gene polymorphic variants can decrease the effects of losartan, reducing active metabolite (E-3174) formation. Study aims to determine the influence of *2 (+430C>T; rs799853) and *3 (+1075A>C; rs1057910) CYP2C9 gene polymorphic variants on the hypotensive and uricosuric effect of losartan on patients with arterial hypertension | ||
| 520 | |a METHODS: Eighty one patients with stage 1-2 arterial hypertension newly diagnosed with ABMP were enrolled in the study. Physicians started losartan treatment and then we measured urine concentration of E-3174/losartan to estimate CYP2C9 activity. After 3-month losartan treatment we compared effectiveness of the therapy with ABPM and plasma uric acid level between carriers of CYP2C9 *1/*1 and CYP2C9 gene polymorphic variants (*2 and *3) | ||
| 520 | |a RESULTS: Carriage of CYP2C9*2 and CYP2C9*3 alleles reduced the hypotensive effect of losartan (p<0.001, OR=8.13 (95% CI, 2.75-23.97)). Analysis of the ABPM data revealed that blood pressure was significantly higher in patients with polymorphic genotypes. There was no significant difference in uric acid level in plasma and losartan and its metabolite concentration in urine between genotypes | ||
| 520 | |a CONCLUSIONS: Carriage of low function polymorphic variants of the CYP2C9 gene (*2 and *3) reduced the hypotensive effect of losartan according to ABPM and don't affect uric acid level in plasma and E-3174/losartan in urine | ||
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CYP2C9 | |
| 650 | 4 | |a APBM | |
| 650 | 4 | |a E-3174 | |
| 650 | 4 | |a losartan | |
| 650 | 4 | |a polymorphisms | |
| 650 | 4 | |a uric acid | |
| 650 | 7 | |a losartan carboxylic acid |2 NLM | |
| 650 | 7 | |a GD76OCH73X |2 NLM | |
| 650 | 7 | |a Losartan |2 NLM | |
| 650 | 7 | |a JMS50MPO89 |2 NLM | |
| 650 | 7 | |a Antihypertensive Agents |2 NLM | |
| 650 | 7 | |a Cytochrome P-450 CYP2C9 |2 NLM | |
| 650 | 7 | |a EC 1.14.13.- |2 NLM | |
| 650 | 7 | |a Uric Acid |2 NLM | |
| 650 | 7 | |a 268B43MJ25 |2 NLM | |
| 650 | 7 | |a Aryl Hydrocarbon Hydroxylases |2 NLM | |
| 650 | 7 | |a EC 1.14.14.1 |2 NLM | |
| 650 | 7 | |a CYP2C9 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.14.13.- |2 NLM | |
| 700 | 1 | |a Boyarko, Alexey V |e verfasserin |4 aut | |
| 700 | 1 | |a Temirbulatov, Ilyas I |e verfasserin |4 aut | |
| 700 | 1 | |a Sychev, Dmitry A |e verfasserin |4 aut | |
| 700 | 1 | |a Akmalova, Kristina A |e verfasserin |4 aut | |
| 700 | 1 | |a Sozaeva, Zhannet A |e verfasserin |4 aut | |
| 700 | 1 | |a Grishina, Elena A |e verfasserin |4 aut | |
| 700 | 1 | |a Mirzaev, Karin B |e verfasserin |4 aut | |
| 700 | 1 | |a Asoskova, Anastasiia V |e verfasserin |4 aut | |
| 700 | 1 | |a Fisenko, Vladimir P |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Drug metabolism and personalized therapy |d 2015 |g 38(2023), 2 vom: 01. Juni, Seite 163-168 |w (DE-627)NLM239517768 |x 2363-8915 |7 nnns |
| 773 | 1 | 8 | |g volume:38 |g year:2023 |g number:2 |g day:01 |g month:06 |g pages:163-168 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1515/dmpt-2022-0115 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 38 |j 2023 |e 2 |b 01 |c 06 |h 163-168 | ||