A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity.
Imidapril is an angiotensin-converting enzyme inhibitor that is widely used in treating hypertension, although the responses vary among individuals. We investigated whether a single nucleotide polymorphism at position -816 of the carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is involved in the responsiveness to imidapril medication. A total of 105 Japanese hypertensives with systolic/diastolic blood pressures (SBP/DBP) of 140/90 mmHg or higher were prescribed 5-10 mg/day of imidapril. At baseline, blood pressure levels were not different between patients with and those without the -816C allele (AA vs. AC+ CC groups). After 8 weeks of treatment, we classified the responders and non-responders based on the decline in their blood pressures, and found that the responder rate was significantly higher in the AC+CC group than in the AA group (p=0.0331). Also, the reduction in SBP was significantly greater in the AC+CC group than in the AA group (24.7+/-11.8 vs. 17.6+/-16.8 mmHg, p=0.0184). Furthermore, an in vitro reporter assay revealed that the -816C construct had significantly higher promoter activity (p<0.0001). These findings suggest that the A(-816)C polymorphism affects the transcriptional activity, and that this may account for the responsiveness to imidapril.
Geshi
Eiichi
E
Third Department of Internal Medicine, Showa University School of Medicine Tokyo, Japan.
Kimura
Tomomi
T
Yoshimura
Mika
M
Suzuki
Hiroshi
H
Koba
Shinji
S
Sakai
Tetsuo
T
Saito
Tsukasa
T
Koga
Atsuro
A
Muramatsu
Masaaki
M
Katagiri
Takashi
T
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D043182:Carboxylesterase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D048289:Imidazolidines / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D048289:Imidazolidines; C065166:imidapril; D043182:Carboxylesterase