Association of CYP450 single nucleotide polymorphisms with the efficacy of epidural ropivacaine during mastectomy.

Abstract

Ropivacaine is frequently used for local anesthesia in the clinic and is metabolized by cytochrome P450 (CYP450) in the liver. CYP450 polymorphisms may alter the therapeutic efficacy of drugs in patients. In this study, we selected six CYP450 polymorphisms from the dbSNP and HapMap databases, using a combination of functional analysis and Tag SNP strategies and examined these polymorphisms for association with the efficacy of epidural ropivacaine in patients during mastectomy. A total of 256 patients with breast cancer received thoracic epidural anesthesia with ropivacaine for elective mastectomy with axillary lymph node clearance. Blood samples from patients were genotyped using the SNaPshot method. We found that patients with rs11636419 AG and GG genotypes required lower doses of epidural ropivacaine than patients with the AA genotype (corrected P = 0.024 and P < 0.001, respectively). Similarly, patients with rs17861162 CG and GG genotypes required lower doses of epidural ropivacaine than those with the CC genotype (corrected P = 0.018 and P < 0.001, respectively). There was no statistically significant association between the other four single nucleotide polymorphisms (SNPs) and total or mean ropivacaine dose, the onset of ropivacaine, or the initial dose of lidocaine. Our present data demonstrate that CYP1A2 SNPs rs11636419 and rs17861162 alter the sensitivity of epidural ropivacaine in patients undergoing breast cancer surgery. As such, detection of these two CYP1A2 SNPs may aid in the development of effective personalized treatments for breast cancer patients.