Receptors and channels: Association between haplotype structure in the genes encoding thermosensitive channels and experimental pain sensitivity in European Americans

Abstract

The objective was to consider the low to moderate heritability estimates of pain sensitivity and large number of related genes, a haplotype map may provide a better tool in investigating the role of genetic factors in pain than single individual polymorphisms. We generated haplotype blocks based on the single nucleotide polymorphisms (SNPs) from δ opioid receptor subtype 1 gene (OPRD1), transient receptor potential V subtype1 gene (TRPV1), transient receptor potential M subtype 8 gene (TRPM8) and ankyrin-like with transmembrane domains 1 gene (ANKTM1). We investigated the association between these haplotype blocks and experimental thermal and cold pain sensitivity in European American population. European American subjects (N=310) provided ratings of sensory intensity for heat stimuli applied to the volar forearm and for a 3 min cold pressor test using a standard 10 cm visual analog scale. For genotyping of genomic DNA, 5' exonuclease allelic discrimination assays were performed. Haplotype frequency of unphased genotypes was inferred using PHASE method and measured linkage disequilibrium by Lewontin's Disequilibrium coefficient, D prime. We identified haplotype blocks, which shows little evidence of recombination OPRD1, TRPV1, TRPM8 and ANKTM1. All the genotypes assessed with GeneStat program assume Hardy-Weinberg Equilibrium. We found a significant relationship between 2 haplotype blocks in ANKTM1 and the cold pain sensitivity in European American population. These data suggest the role of genetic factors based on haplotype blocks in experimental pain sensitivity in humans and support the role of ANKTM1 in the perception of experimental cold pain.