A new genetic locus cosegregating with blood pressure in F2 progeny obtained from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats

Abstract

Background: Segregation studies using genomic polymorphisms on F2 progeny obtained from hypertensive rat models showed that a putative hypertensive gene is located close to the angiotensin converting enzyme (ACE) gene. However, it was suggested that additional major genes should contribute to the pathogenesis of hypertension.

Methods: F2 rats were obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats of Izumo colony. Blood pressure was measured with a photoelectronic oscillometric tail-cuff method before and during salt loading. Genomic DNA was extracted from livers and digested with HaeIII or Rsal. DNA fingerprinting was performed with 26 32P-labelled human variable number of tandem repeats markers.

Results: Eighty-seven fingerprint bands polymorphic between SHRSP and WKY were obtained. When the distribution of these bands in the F2 progeny was studied, one fingerprint band (1/MCT96.1) showed a distorted distribution between the high- and low-blood pressure subpopulations of the F2 rats, suggesting that the band cosegregated with blood pressure. When blood pressure was compared between the F2 rats with [(+) rats] and without [(-) rats] the 1/MCT96.1 band, it was found that (-) rats had significantly higher basal and salt-loaded blood pressures than (+) rats. The 1/MCT96.1 locus was also shown to have no positive linkage with the ACE locus.

Conclusion: The present study showed that examination of the allele distribution between subpopulations with extreme phenotype can be used in the screening of loci cosegregating with blood pressure. Furthermore, a locus not in the ACE region, showing cosegregation with blood pressure in F2 progeny from SHRSP and WKY rats, was found.