TY - JOUR
T1 - Genetic mapping of blood pressure quantitative trait loci in Milan hypertensive rats
AU - Zagato, Laura
AU - Modica, Rossana
AU - Florio, Monica
AU - Torielli, Lucia
AU - Bihoreau, M. T.
AU - Bianchi, Giuseppe
AU - Tripodi, Grazia
PY - 2000
Y1 - 2000
N2 - In a previous study, by using a candidate gene approach, we detected in both Milan hypertensive rats and humans a polymorphism in the α-adducin gene (ADD1) that was associated with blood pressure and renal sodium handling. In the present study, a genomewide search with 264 informative markers was undertaken in 251 (Milan hypertensive strain x Milan normotensive strain) F2 rats to further investigate the contribution of the adducin gene family (Add1, Add2, and Add3) and to identify novel quantitative trait loci (QTLs) that affect blood pressure. The influence of 2 different methods of blood pressure measurement, the intracarotid catheter and the tail-cuff method, was also evaluated. We found evidence that QTLs affected systolic blood pressure (SBP) measured at the carotid (direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chromosome 14 on Add1 locus (LOD=3.2). A QTL for SBP measured at the tail (indirect SBP) was found on rat chromosome 10 around D10Rat33 (LOD=5.0). All of these QTLs identified chromosomal regions not detected in other rat studies and harbor genes (Na+/H+ exchanger A3; α-adducin; α(1B)-adrenergic receptor) that may be involved in blood pressure regulation. Therefore, these findings may be relevant to human hypertension, also in consideration of the biochemical and pathophysiological similarities between MHS and a subgroup of patients of primary hypertension, which led to the identification of α-adducin as a candidate gene in both species.
AB - In a previous study, by using a candidate gene approach, we detected in both Milan hypertensive rats and humans a polymorphism in the α-adducin gene (ADD1) that was associated with blood pressure and renal sodium handling. In the present study, a genomewide search with 264 informative markers was undertaken in 251 (Milan hypertensive strain x Milan normotensive strain) F2 rats to further investigate the contribution of the adducin gene family (Add1, Add2, and Add3) and to identify novel quantitative trait loci (QTLs) that affect blood pressure. The influence of 2 different methods of blood pressure measurement, the intracarotid catheter and the tail-cuff method, was also evaluated. We found evidence that QTLs affected systolic blood pressure (SBP) measured at the carotid (direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chromosome 14 on Add1 locus (LOD=3.2). A QTL for SBP measured at the tail (indirect SBP) was found on rat chromosome 10 around D10Rat33 (LOD=5.0). All of these QTLs identified chromosomal regions not detected in other rat studies and harbor genes (Na+/H+ exchanger A3; α-adducin; α(1B)-adrenergic receptor) that may be involved in blood pressure regulation. Therefore, these findings may be relevant to human hypertension, also in consideration of the biochemical and pathophysiological similarities between MHS and a subgroup of patients of primary hypertension, which led to the identification of α-adducin as a candidate gene in both species.
KW - Genes
KW - Hypertension, essential
KW - Rats, inbred strains
UR - http://www.scopus.com/inward/record.url?scp=0033711961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033711961&partnerID=8YFLogxK
M3 - Article
C2 - 11082136
AN - SCOPUS:0033711961
VL - 36
SP - 734
EP - 739
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 5
ER -