The role of the ADRA2A C1291G genetic polymorphism in response to dexmedetomidine on patients undergoing coronary artery surgery.

ABSTRACT

The existence of interindividual drug response variability has been known for a long time. Individual susceptibility which might cause toxicity or inadequate treatment is important in drug therapy. Genetic polymorphisms in genes responsible for drug response are expected to be useful in keeping track of differences among individuals. Dexmedetomidine is a sedative drug, whose use in intensive care unit patients was confirmed by USA-Food Drug Administration (FDA) by the end of 1999. It was proven that dexmedetomidine shows its clinic effect via the α(2)-AR. However, to the best of our knowledge, to date, there is no investigation in clinic indicating the relation between dexmedetomidine and α(2A)-AR gene polymorphism. The aim of our study was to investigate the association between the effect of α(2A)-Adrenergic Receptor (ADRA2A) C-1291G gene polymorphism in the promoter region of the candidate gene and clinical effects (sedative and haemodynamics effects) of dexmedetomidine. One hundred and ten patients undergoing coronary artery surgery were prospectively studied. Anesthetic technique was standardized with fentanyl, midazolam and rocuronium bromide. Patients were monitorized with Bispectral Index (BIS) monitor in addition to the routine invasive haemodynamic monitorization in the operation room. The Ramsay Sedation Scale was also used in order to determine the sedation level just arriving to Intensive Care Unit (ICU). The genotyping of ADRA2A C1291G was done by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). We found the frequencies of C1291C, C1291G and G1291G genotypes, as 43.6, 45.5 and 10.9%, respectively. Patients who carry variant genotype had higher BIS and Ramsay Sedation Scores, indicating a longer period for falling asleep. The results of our study are promising, considering the association between ADRA2A polymorphism and response to dexmedetomidine. However, further investigations on other ADRA2A locus or haplotypes might be useful to clarify the relation between this gene and dexmedetomidine activity.