Genetic mapping of blood pressure quantitative trait loci in Milan hypertensive rats

In a previous study, by using a candidate gene approach, we detected in bot h Milan hypertensive rats and humans a polymorphism in the alpha -adducin g ene (ADD1) that was associated with blood pressure and renal sodium handlin g. In the present study, a genomewide search with 264 informative markers w as undertaken in 251 (Milan hypertensive strain X Milan normotensive strain ) F2 rats to further investigate the contribution of the adducin gene famil y (Add1, Add2, and Add3) and to identify novel quantitative trait loci (QTL s) that affect blood pressure, The influence of 2 different methods of bloo d pressure measurement, the intracarotid catheter and the tail-cuff method, was also evaluated. We found evidence that QTLs affected systolic blood pr essure (SBP) measured at the carotid (direct SEP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chro mosome 14 on Add1 locus (LOD = 3.2). A QTL for SEP measured at the tail (in direct SEP) was found on rat chromosome 10 around D10Rat33 (LOD = 5.0). All of these QTLs identified chromosomal regions not detected in other rat stu dies and harbor genes (Na+/H+ exchanger A3; alpha -adducin; alpha (1B)-adre nergic receptor) that may be involved in blood pressure regulation. Therefo re, these findings may be relevant to human hypertension, also in considera tion of the biochemical and pathophysiological similarities between MHS and a subgroup of patients of primary hypertension, which led to the identific ation of cu-adducin as a candidate gene in both species.