Comparison of alpha 2a gene C-1291G polymorphism and dexmedetomidin's sedative and haemodynamics effects.

The existence of variations in drug response have been known for a long time. Firstly, it was discovered that the activities of drug metabolizing enzymes show interindividual dissimilarity. However, nowadays, it is clear that not only enzymes but carriers and receptors also have genetic variations. In the scope of the growing pharmacogenetics knowledge, mutations in the gene coding region for enzymes, carrier proteins and receptors have been found. Since one-third of all drugs in market are adrenergic agonist and antagonist, the pharmacogenetic importance of the adrenergic system is obvious. There are many studies indicating the association between drug-receptor and disease-receptor interractionDexmedetomidine is a sedative drug, whose use in intensive care units patients confirmed by USA-Food Drug administration (FDA) by the end of 1999. The affinity of dexmedetomidine to ?2- receptor is eight times higher than that of clonidine. ?2 -agonistic effect of dexmedetomidine is 1620 times higher than its ?1-agonistic effect. It was proven that dexmedetomidine indicates its clinic effect via ?2A-AR. There has been no investigation in clinic indicating the association with dexmedetomidine and ?2A-AR gene polymorphismIn the present study, the association with ?2A-AR C-1291G gene polymorphism and the effect of dexmedetomidine was investigated. Blood samples for assessment of ?2A-AR C-1291G gene polymorphism were collected from 110 patients undergoing Coronary Artery Bypass Graft Surgery and right after the operation the patients were followed for wakefulness by BIS monitorization and Ramsay sedation scaleWe found the frequencies genotypes WT (CC); 43,6% (n=48), heterozygous (CG); 45,5% (n=50) and variant (GG); 10,9 % (n=12). Our results showed that there was a relationship between ?2A-AR C-1291G gene polymorphism and hiperlipedemia. All patients carrying G-1291G variant genotype were hiperlipidemic and there was a statistical significance compared to other genotypes (C129G and C1291C) (p<0,05). We observed similar results with blood-glucose levels; patients with mutant homozygous genotypes had higher blood-glucose levels than patients with heterozygous and wild genotypes (p<0,05Patients with mutant homozygous are fallen sleep slower than patients with heterozygous and wild genotypes in terms of BIS and Ramsay Sedation Scores, however the results were not statistically significant. There was not a significant association with systolic and diastolic artery pressure and heartbeat with ?2A-AR C-1291G gene polymorphismIn conclusion, there was no association between ?2A-AR C-1291G polymorphism and clinic effects of dexmedetomidine. Further investigations are needed with larger sample size in combination with other gene polymorphisms.