(426) Genetics and drug response: study on the role of genetics in analgesic response variations in chronic pain patients taking hydrocodone

Opioids are one of the most prescribed classes of medications in the US. Though it is known that different patients respond to medications differently due to genetic variations, little is known about the genes that may be responsible for this variation. The objective of this study is to determine the role of genetics in individual analgesic response variations to Hydrocodone use. This study included 1219 pain subjects (males 509, females 710) across 30 Clinical research sites in the US. The analgesic effect of the hydrocodone was recorded using the Proove Medication Efficacy Differentiation (MED) Scale (A scale of 1-5 to measure efficacy of a drug). Subjects using other opioid medication(s) in addition to Hydrocodone were excluded from this study. Subjects were genotyped with the proprietary Proove Narcotic Risk Genetics Profile using TaqMan SNP genotyping assays (Life Technologies, Carlsbad, CA). It consists of a panel of 12 SNPs in genes encoding for proteins expressed in the mesolimbic reward pathway. These genes include: 5HT2a, 5-HTTL, COMT, ANKK1/DRD2, DRD1, DRD4, DAT, DBH, MTHFR, OPRK1, GABA-A receptor gamma2, and OPRM1.A Kruskal Wallis test using SPSS v21 found a significant relationship between DBH (rs1611115) C/T and Hydrocodone response (p= 0.04). A Mann-Whitney test (p= 0.032) found a more robust relationship between DBH -1021 C/T and response to hydrocodone using the over dominant model. Further analysis using an ordinal regression (p= 0.032) showed that C/T variation is more associated with subjects with good response to Hydrocodone while T/T and C/C were more associated with subjects with poor response to Hydrocodone (p=0.032). This study suggests that genetic variations may play a role in observed differences in response to Hydrocodone usage. Also, it showed that a heterozygous advantage may exist that influences response to hydrocodone. Study was supported by Proove Biosciences.