Evidence for association of two variants of the nociceptin/orphanin FQ receptor gene OPRL1 with vulnerability to develop opiate addiction in Caucasians.
OBJECTIVE
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).


CONCLUSIONS
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.
Briant
Judith A
JA
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York 10065, USA.
Nielsen
David A
DA
Proudnikov
Dmitri
D
Londono
Douglas
D
Ho
Ann
A
Ott
Jurg
J
Kreek
Mary Jeanne
MJ
D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009293:Opioid-Related Disorders / Q000235:genetics*; D011957:Receptors, Opioid / Q000235:genetics*; D044465:White People / Q000235:genetics*; D000094942:Nociceptin Receptor
D017931:DNA Primers; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human