A regulatory variation in OPRK1, the gene encoding the -opioid receptor, is associated with alcohol dependence
Human Molecular Genetics Advance Access published online on March 4, 2008


Variations in OPRK1, which encodes the -opioid receptor, are associated with the risk for alcohol dependence.

Sequencing DNAs with higher and lower risk haplotypes revealed an insertion/deletion (indel) with a net addition of 830 bp located 1986 bp upstream of the translation start site (1389 bp upstream of the transcription start site).

We demonstrated that the upstream region extending from -1647 to -10 bp or from -2312 to -10 bp (relative to the translation start site) could function as a promoter in transient transfection assays. We then determined that the presence of the indel reduced transcriptional activity by half.

We used a PCR assay to genotype individuals in 219 multiplex alcohol dependent families of European American descent for the presence or absence of this indel.

Family-based association analyses detected significant evidence of association of this insertion with alcoholism; the longer allele (with the indel), which had lower expression, is associated with higher risk for alcoholism.

This indel is, therefore, a functional regulatory variation likely to explain at least part of the association of OPRK1 with alcohol dependence.

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