The ABCB 1 , rs9282564, AG and TT Genotypes and the COMT , rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction

Sudden death due to acute intoxication occurs frequently in patients with opioid addiction ( OA ). To examine whether certain genotypes were associated with this, we examined the frequencies of 29 SNP s located in candidate genes related to opioid pharmacology: ABCB 1 , OPRM 1 , UGT 2B7 , CYP 3A5 , CYP 2B6 , CYP 2C19 , CYP 2D6 , COMT , KCNJ 6 and SCN 9A in 274 deceased patients with OA ( DOA ), 309 living patients with OA ( LOA ) and in 394 healthy volunteers ( HV ). The main hypothesis of the study was that subjects homozygous for the variant 3435T in ABCB 1 (rs1045642) occur more frequently in DOA than in LOA and HV because morphine and methadone more readily cross the blood barrier in these subjects due to a lower efflux transporter activity of the ABCB 1 (p‐glycoprotein) transporter. Our results did not support this hypothesis, because no statistically significant difference ( p = 0.506) in the frequency of the TT genotype of rs1045642 was observed between the DOA , LOA and HV cohorts. However, for another ABCB 1 variant, rs9282564, we found that the frequencies of the AG and TT genotypes were 13, 21 and 25% in DOA , LOA and HV , respectively, and after correcting for age, sex and multiple testing, the differences between DOA and LOA were statistically significantly different ( p = 0.027). The COMT rs4680 AA genotype frequencies were 25%, 35% and 31% in DOA , LOA and HV , respectively, and the difference between DOA and LOA was also statistically significant ( p = 0.0028). In conclusion, this study generated two hypotheses suggesting possible associations of a reduced risk of death and carrying, respectively, the ABCB 1 rs9282564 AG and TT genotypes and the COMT rs4680 AA genotype among patients with OA . These findings should be confirmed in independent cohorts, and if a causal relationship between these variants and fatal poisoning in OA is confirmed, then it may be possible at least in theory to personalize prevention of sudden death in this patient group.