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(Hypertension. 2001;38:786.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Neither the New Zealand Genetically Hypertensive Strain nor Dahl Salt-Sensitive Strain Has an A1079T Transversion in the 1 Isoform of the Na⁺,K⁺-ATPase Gene

Ross Barnard; Greg Kelly; Sergio Otterlei Manzetti; Eugenie L. Harris

From the Department of Biochemistry, University of Queensland (R.B.), Brisbane, Australia; School of Life Sciences and Cooperative Research Centre for Diagnostic Technologies, Queensland University of Technology (G.K., S.M.), Brisbane, Australia; and Department of Surgery, University of Otago (E.L.H.), Dunedin, New Zealand.

Correspondence to Dr Eugenie L. Harris, Department of Surgery, University of Otago, Dunedin Public Hospital, Academic Wing, PO Box 913, Dunedin, New Zealand. E-mail jean.harris{at}stonebow.otago.ac.nz

Abstract—— A putative 1079AT mutation in the 1 isoform of the Na⁺, K⁺-ATPase (Atp1a1) gene of the Dahl salt-sensitive rat inbred by John Rapp (SS/Jr) strain was projected to cause a conformation change in the membrane hydrophobic region of the protein product, possibly resulting in hypertension. The existence of the mutation was challenged, but the challenge was apparently rebutted. The New Zealand genetically hypertensive (GH) rat is known to have a blood pressure quantitative trait locus on chromosome 2 containing the gene for the ATPase. Thus, we sought to determine whether the GH rat carried the 1079AT transversion. We chose a method, first nucleotide change analysis, that can detect point mutations in a mixed population of polymerase chain reaction (PCR) products, even in the presence of PCR bias, and confirmed our analysis by restriction enzyme digestion of PCR products. To ensure the validity of our analyses, we used site-directed mutagenesis to create positive controls containing the mutation. Surprisingly, we found that neither the GH nor the SS/Jr strain had the A1079T transversion. Indeed, the transversion was not found in any strain tested. As an incidental observation, we have sequenced the intron preceding the exon containing the putative A1079T transversion. Within this intron, a single-base C/T polymorphism was observed at base 132. Our results definitively eliminate the putative A1079T transversion in Atp1a1 as a causative factor underlying hypertension in the GH, spontaneously hypertensive, and SS/Jr rat strains and indicate that alternative candidate genes in the region defined by the chromosome 2 hypertension quantitative trait locus should be examined.

Key Words: Na⁺-K⁺-transporting ATPase • genetics • blood pressure • polymerase chain reaction • mutation

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