Single nucleotide polymorphism (SNP) discovery of human trace amine associated receptors TAAR1 and TAAR9 and their possible role in vasomotor tone

Abstract

Responses to trace amines (tyramine, β‐phenylethylamine, tryptamine, and octopamine found in tissues in low nM concentrations) are mediated by trace amine‐associated receptors (TAARs), which are composed of nine G protein‐coupled receptors. Because little is known about genetic variations in TAARs, we assessed for SNPs in the coding region of TAAR1 and TAAR9 from 52 subjects [28 normotensive (NT)/ 24 hypertensive (HT), 42 male/10 female, 29 Caucasian/23 African American, mean age 47±2]. We identified six TAAR1 SNPs (three found only in HTs) and six TAAR9 SNPs including AAA‐>TAA in Lys61 that causes a premature stop codon. Analysis of the association of TAAR1/TAAR9 SNPs and venoconstriction in 50 healthy individuals [30 male/20 female, mean age 25±7] in response to tyramine infusion into dorsal hand veins revealed that subjects who have one of two TAAR9 SNPs (Asn3Asn or Ala278Thr) have more vasoconstriction than do wild‐type individuals. In spite of its high allelic frequency (22%), the TAAR9 codon 61 SNP was not associated with venoconstrictor responses. These results indicate that both TAARs are polymorphic but most SNPs (other than TAAR9 codon 61) are rare. The data suggest that normotensive and hypertensive subjects have differential expression of TAAR1 and TAAR9 SNPs and that particular TAAR9 SNPs (e.g., Asn3Asn and Ala278Thr) may contribute to enhanced venoconstrictive responses. (Supported by NIH grants)