原发性和继发性肾脏疾病患者的CYP2C9基因型及对氯沙坦的药效学反应
CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases.
作者信息
Joy Melanie S, Dornbrook-Lavender Kimberly, Blaisdell Joyce, Hilliard Tandrea, Boyette Tammy, Hu Yichun, Hogan Susan L, Candiani Corina, Falk Ronald J, Goldstein Joyce A
机构信息
Division of Nephrology and Hypertension, School of Medicine, UNC Kidney Center, University of North Carolina, Chapel Hill, NC, USA.
出版信息
Eur J Clin Pharmacol. 2009 Sep;65(9):947-53. doi: 10.1007/s00228-009-0707-7. Epub 2009 Aug 11.
BACKGROUND
Losartan is used for anti-proteinuric as well as blood pressure effects in chronic kidney disease (CKD). It is metabolized by cytochrome P450 (CYP) 2C9 to active E-3174. Single nucleotide polymorphisms in CYP2C9 that reduce catalytic activity could reduce clinical benefits.
AIM
The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasian patients prescribed losartan.
METHODS
Differences between baseline and 6-month follow-up outcomes were compared by CYP2C9 genotypes in 59 patients using unpaired t test or Mann-Whitney U test.
RESULTS
Primary renal disease patients had a trend toward less favorable antiproteinuric response (-31.7 +/- 156 vs. -125 +/- 323%; p = 0.123) when carrying variant alleles. Patients with secondary renal diseases had less favorable diastolic blood pressure (9.8 +/- 16.0 vs. -3.2 +/- 10.6 mmHg; p = 0.043) and systolic blood pressure (16.2 +/- 27.1 vs. -5.5 +/- 17.5 mmHg; p = 0.044) with CYP2C9 variants.
CONCLUSION
These preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan.
背景
氯沙坦用于慢性肾脏病（CKD）的抗蛋白尿及降压治疗。它经细胞色素P450（CYP）2C9代谢为活性产物E - 3174。CYP2C9中降低催化活性的单核苷酸多态性可能会降低临床疗效。
目的
本研究旨在确定CYP2C9变异等位基因（2和3）是否会改变接受氯沙坦治疗的白种人患者的尿蛋白排泄、肾小球滤过率和血压。
方法
采用不成对t检验或Mann - Whitney U检验，比较59例患者按CYP2C9基因型分组的基线和6个月随访结果之间的差异。
结果
携带变异等位基因时，原发性肾病患者的抗蛋白尿反应趋势较差（-31.7±156 vs. -125±323%；p = 0.123）。CYP2C9变异的继发性肾病患者的舒张压（9.8±16.0 vs. -3.2±10.6 mmHg；p = 0.043）和收缩压（16.2±27.1 vs. -5.5±17.5 mmHg；p = 0.044）较差。
结论
这些初步结果表明，CYP2C9基因型可能会影响接受氯沙坦治疗的白种人CKD患者的蛋白尿和血压。
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