Endocrine Abstracts

As a lingering, often deteriorating brain disease, addiction causes neurotic drug seeking and utilization along with injurious significances to the addicts and to those living around them. Biological, genetic and a number of intrinsic and extrinsic environmental constituents are most vital in entire risk factors of drug addiction. Among addictive drugs opioid dependence is considered as the most deliberated drug abuse disorder and a major social dilemma worldwide. Opioids induce their action through opioid receptors. Among opioid receptors, the δ receptor encoded by OPRDI gene is involved in opioid addiction susceptibility. Genetic associations of polymorphisms in OPRD1 gene e.g. rs569356 with heroin addiction are being reported in different world populations. Opioid addiction has been strongly linked to stress conditions which increases craving for drug, development of addictive behaviors, as well as relapse to opioid use which in turn accelerates the major component of stress response system, Hypothalamus Pituitary Adrenal axis (HPA axis). Cortisol, as a final product of HPA axis of stress response in humans, is evaluated in blood serum of opioid addicts and thus could be used as a marker of stress response. The relationship between cortisol levels and rs569356 SNP in opioid addicts has not been explored yet. Keeping with the crucial roles of OPRDI receptor in drug addiction and cortisol as a stress response, present study was designed to investigate association of the risk allele of rs569356 OPRDI variant with stress response in Pakistani opioid addicts. Whole blood samples from opioid addicts were collected for the extraction of genomic DNA and cortisol from serum. Genotyping of rs569356 was carried out by using allele specific PCR while cortisol levels were estimated by approaching ELISA. Allele frequencies were estimated through χ²-test while association analyses were performed through regression models. Our results have shown high frequency of minor G allele of rs569356 (0.42) in drug addicts while the ancestral ‘A’ allele frequency was 0.58. Social and addictive behaviors including family history, guilt of addictive habits, family issues, and disturbance in daily routine significantly associated with drug addiction (P=0.000). The minor allele G of rs569356 SNP lacked association with opioid addiction but showed strong correlation with serum cortisol levels Our results confirm the role of minor G allele as risk marker of opioid addiction in Pakistani population through its role in elevating the stress responses (cortisol).