The haplotype structure in the gene encoding the delta-opioid receptor in humans

Abstract

Considering the low to moderate heritability estimates of pain sensitivity and huge number of related genes, a haplotype block may provide a better tool in investigating the role genetic variations in pain and analgesic response due to single nucleotide polymorphism (SNPs). Our previous findings suggested that SNPs on delta-opioid receptor subtype 1 (OPRD1) gene contribute to variations in experimental pain sensitivity. Hence, we investigated the haplotype block structure in OPRD1 gene in 313 unrelated human subjects that include European American (EA), Asian (ASN), Hispanic (HIS) and African (AFR) American. We assayed OPRD1 genotypes for 9 single nucleotide polymorphisms (SNPs) loci using genomic DNA 5′ exonuclease allelic discrimination assays. Haplotype frequency of unphased genotypes was inferred using PHASE method and measured linkage disequilibrium by Lewontin's Disequilibrium coefficient, D prime (> 0.75). We identified haplotype blocks, which shows little evidence of recombination, in the range of 0.79 and 16.4 kilo bases in different ethnic groups studied. AFR population exhibited very small and distinct block structure than the other ethnic groups. HIS and ASN population showed different combination of block structure but both shared structures with EA population. EA population was separate from other groups by having most of the blocks. In our previous findings we observed higher cold withdrawal time (CWT) for EA. Given this association, higher CWT by EA may be due in part to this distinct block structure of the OPRD1 gene. Thus, differences in haplotype block structure in different population might provide insights into individual variation in pain ratings and the response to opioid drugs. Clinical Pharmacology & Therapeutics (2004) 75, P4–P4; doi: 10.1016/j.clpt.2003.11.015