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 E, Kimura T, Yoshimura M, Suzuki H, Koba S, Sakai T, Saito T, Koga A, Muramatsu M, Katagiri T (2005) A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity Hypertens Res28: 719-25
Geshi E, Kimura T, Yoshimura M, Suzuki H, Koba S, Sakai T, Saito T, Koga A, Muramatsu M, Katagiri T (2005) Hypertens Res28: 719-25
