Investigation of the phenylethanolamine N-methyltransferase gene as a candidate gene for hypertension.

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 Pnmts 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.

Duke Scholars

Author Victor J. Dzau Medicine, Cardiology