Objectives: The OPRL1 gene encodes the nociceptin/orphanin FQ receptor, which plays a role in regulating tolerance and behavioral responses to morphine. However, there is limited information on whether variants of OPRL1 are associated with vulnerability to develop opiate addiction. In this study, we examined five variants of OPRL1 and their role in determining vulnerability to develop opiate addiction.
Methods: We recruited 447 individuals: 271 former severe heroin addicts and 176 healthy controls. Using a 5′-fluorogenic exonuclease assay, we genotyped individuals at five variants in OPRL1. It was then determined whether there was a significant association of allele, genotype, or haplotype frequency with vulnerability to develop opiate addiction.
Results: When the cohort was stratified by ethnicity, we found that, in Caucasians but not in African–Americans or Hispanics, the allele frequency of rs6090041 and rs6090043 were significantly associated point-wise with opiate addiction (P=0.03 and 0.04, respectively). Of the haplotypes formed by these two variants, one haplotype was found to be associated with protection from developing opiate addiction in both African–Americans (point-wise P=0.04) and Caucasians (point-wise P=0.04), and another haplotype with vulnerability to develop opiate addiction in Caucasians only (P=0.020).
Conclusion: This study provides evidence for an association of two variants of the OPRL1 gene, rs6090041 and rs6090043, with vulnerability to develop opiate addiction, suggesting a role for nociceptin/orphanin FQ receptor in the development of opiate addiction.
aLaboratory of the Biology of Addictive Diseases
bLaboratory of Statistical Genetics, The Rockefeller University, New York
cMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Michael E. DeBakey V.A. Medical Center, Houston, Texas, USA
dBeijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Correspondence to Professor Mary Jeanne Kreek, MD, Laboratory of the Biology of Addictive Diseases, The Rockefeller University, Box 171, 1230 York Avenue, NY 10065, USA
Tel: +1 212 327 8490; fax: +1 212 327 8574; e-mail: firstname.lastname@example.org
Received 11 September 2008 Revised 27 August 2009 Accepted 13 September 2009