Evaluation of the angiotensin II receptor AT1B gene as a candidate gene for blood pressure.
OBJECTIVE
To answer two specific questions concerning the possible role played by the angiotensin II receptor AT1B (AT1B) locus in genetic hypertension. First, do alleles at the AT1B locus cosegregate with blood pressure in F2 populations in the rat and, if so, is this due to AT1B or a closely linked quantitative trait locus (QTL)? Secondly, are there any significant nucleotide differences between the coding regions of the AT1B gene of the inbred Dahl salt-sensitive (SS/Jr) strain and various control strains, or between the Lyon hypertensive (LH) strain the Lyon normotensive (LN) strain?


METHODS
The first objective was achieved by studying several F2 rat populations and by analyzing DNA markers around the AT1B locus. The second objective was accomplished by amplifying the AT1B coding regions by polymerase chain reaction from the genomic DNA, and by sequencing the relevant coding regions of the AT1B genes.


RESULTS
In two F2 populations involving the SS/Jr rat, AT1B cosegregated only weakly with systolic blood pressure. Also, nucleotide differences resulting in conservative changes in three amino acids were detected between the coding region of the SS/Jr AT1B allele and the AT1B alleles of the several control strains. No nucleotide differences were found in the coding regions of the AT1B alleles between the LH and LN strains.


CONCLUSIONS
There appeared to be a QTL which had a minor effect on blood pressure, located near the AT1B locus on rat chromosome 2. However, the AT1B gene itself is not supported as the candidate gene for causing blood pressure differences, because no nucleotide changes in the coding region that were functionally meaningful or concordant with the cosegregation analysis were detected.
Deng
A Y
AY
Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo 43699.
Rapp
J P
JP
D000804:Angiotensin II / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D002874:Chromosome Mapping; D017124:Conserved Sequence; D015342:DNA Probes; D015698:Genomic Library; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000235:genetics*; D017421:Sequence Analysis; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage
D015342:DNA Probes; D011945:Receptors, Angiotensin; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II