Genetic mapping of a new heart rate QTL on chromosome 8 of spontaneously hypertensive rats.
BACKGROUND
Tachycardia is commonly observed in hypertensive patients, predominantly mediated by regulatory mechanisms integrated within the autonomic nervous system. The genetic loci and genes associated with increased heart rate in hypertension, however, have not yet been identified.


METHODS
An F2 intercross of Spontaneously Hypertensive Rats (SHR) x Brown Norway (BN) linkage analysis of quantitative trait loci mapping was utilized to identify candidate genes associated with an increased heart rate in arterial hypertension.


RESULTS
Basal heart rate in SHR was higher compared to that of normotensive BN rats (365 +/- 3 vs. 314 +/- 6 bpm, p < 0.05 for SHR and BN, respectively). A total genome scan identified one quantitative trait locus in a 6.78 cM interval on rat chromosome 8 (8q22-q24) that was responsible for elevated heart rate. This interval contained 241 genes, of which 65 are known genes.


CONCLUSIONS
Our data suggest that an influential genetic region located on the rat chromosome 8 contributes to the regulation of heart rate. Candidate genes that have previously been associated with tachycardia and/or hypertension were found within this QTL, strengthening our hypothesis that these genes are, potentially, associated with the increase in heart rate in a hypertension rat model.
Silva
Gustavo J J
GJ
Department of Medicine-LIM13, Heart Institute (InCor), University of São Paulo Medical School, Av, Dr, Enéas de Carvalho Aguiar, 44, 10o andar, 05403-000, São Paulo, SP, Brazil. gjjusto@usp.br
Pereira
Alexandre C
AC
Krieger
Eduardo M
EM
Krieger
José E
JE
D000818:Animals; D001794:Blood Pressure; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006339:Heart Rate / Q000235:genetics*; D008297:Male; D011247:Pregnancy; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR
D005819:Genetic Markers