Investigation of the Phenylethanolamine N -Methyltransferase Gene as a Candidate Gene for Hypertension

Abstract

Abstract Genetic mapping studies have located a gene, Bp1 , that accounts for approximately 30% of the genetic variation in the stroke-prone spontaneously hypertensive rat (SHRSP) to a region on chromosome 10 containing the angiotensin-converting enzyme gene. In humans, the gene encoding phenylethanolamine N -methyltransferase (PNMT) was localized near the angiotensin-converting enzyme gene on human chromosome 17. Since most of human chromosome 17 is known to be homologous to rat chromosome 10 and PNMT is known to play a role in blood pressure homeostasis, we reasoned (1) that the rat gene encoding PNMT ( Pnmt ) may reside on chromosome 10 within the confidence interval containing Bp1 and (2) that Pnmt is a good candidate gene for Bp1. With the use of a somatic cell hybrid panel and genetic mapping techniques, Pnmt mapped within the confidence interval that contains Bp1 . To examine further this possibility of Pnmt as a candidate for Bp1 , we cloned and characterized Pnmt s of the original parental strains, the Wistar-Kyoto rat and SHRSP from the Heidelberg colony. We did not identify any sequence differences between the Wistar-Kyoto rats and SHRSP in the primary structure, in 1077 bp of the 5′-flanking region, or in the 256-bp 3′-end region, making Pnmt an unlikely gene for the genetic basis of salt-loaded hypertension.