Variant detection at the delta opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence

The three opioid receptor genes, and in particular the mu and delta loci (O PRM1 and OPRD1, respectively), an compelling candidates to influence risk f or substance dependence. Previous study of a variant at the OPRD1 locus, T9 21C, has shown association with opioid dependence. This variant does not al ter protein sequence, and could not be directly responsible for a physiolog ic effect. We sequenced the OPRD1 coding region in six individuals with dif fering T921C alleles, to identify new common variants more likely to explai n the association with phenotype. We identified one novel variant in exon 1 , 80T --> G, which predicts a change in amino acid sequence from phenylalan ine (80T) to cysteine (80G) (F27C). We present here basic population geneti cs of this variant, and population genetic data for the T921C variant. We f ound significant differences in allele frequency between populations, and a maximum frequency of the 80G allele of 9%, in each of two European populat ions. This variant could contribute to the previously reported association results.