ASSOCIATION OF THE BRAIN NATRIURETIC PEPTIDE GENE WITH BLOOD-PRESSUREAND HEART-WEIGHT IN THE RAT

1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP ) are important in the control of body fluid homeostasis, blood pressu re (BP) regulation and vascular remodelling, The genes for these pepti des may, therefore, be involved in the pathogenesis of genetic hyperte nsion, We have previously described a quantitative trait locus (QTL) f or BP in the ANP gene region on rat chromosome 5, We have now assessed the possibility that this QTL lies at the closely linked BNP locus. 2 . Intra-arterial BP and heart weight were measured in 12-week-old (n = 207) and 24-week-old (n = 88) F2 rats derived from crosses between Wi star-Kyoto normotensive rats and spontaneously hypertensive rats, We d esigned polymerase chain reaction primers to amplify a microsatellite in the BNP gene from genomic DNA, Analysis of variance was used for co segregation analysis, Linkage mapping and localization of QTL was perf ormed using the Mapmaker computer package. 3. A significant correlatio n was found between genotype for the BNP gene and systolic BP (P < 0.0 01) in 12-week-old rats, The ANP gene, but not the BNP gene, was assoc iated with systolic BP in 24 week rats, There was no segregation of he art weight with BNP genotype at 12 or 24 weeks of age, The BNP gene ma pped approximately 20 cM from the ANP gene in our rat hybrids, away fr om the previously described QTL, There was evidence for a second BP lo cus near to but distinct from the BNP gene. 4. These results suggest t hat BP QTL are present in the natriuretic peptide gene region but that the ANP and BNP genes themselves have no major effect on BP in this c ross.