Models of human disease have long been used to understand the basic pathophysiology of disease and to facilitate the discovery of new therapeutics. However, as long as models have been used there have been debates about the utility of these models and their ability to mimic clinical disease at the phenotypic level. The application of genetic studies to both humans and model systems allows for a new paradigm, whereby a novel comparative genomics strategy combined with phenotypic correlates can be used to bridge between clinical relevance and model utility. This study presents a comparative genomic map for "candidate hypertension loci in humans" based on translating QTLs between rat and human, predicting 26 chromosomal regions in the human genome that are very likely to harbor hypertension genes. The predictive power appears robust, as several of these regions have also been implicated in mouse, suggesting that these regions represent primary targets for the development of SNPs for linkage disequilibrium testing in humans and/or provide a means to select specific models for additional functional studies and the development of new therapeutics.

This study provides further evidence to support the role of MMP-9 in the pathogenesis of AAA, and indicates that the MMP9 C-1562T functional polymorphism may represent a genetic component contributing to susceptibility to this vascular disease.

This study provides no evidence that the T variant of MTHFR is associated with susceptibility to AAA, CAD or PVD. It may, however, be a contributory factor in AAA severity as indicated by aneurysm size.

The selection against the 4G4G genotype in the familial AAA population may indicate a role for PAI in the development of AAA in this population.

Based on the published cDNA base sequence for the (anonymous) SA gene, a polymerase-chain-reaction (PCR) product from the SA gene was obtained from a Dahl salt-sensitive rat kidney cDNA library. Compared to the published sequence, this product had a 102 base pair insert in the 3' end of the cDNA, probably as the result of alternate mRNA splicing. A StuI restriction fragment length polymorphism detected three alleles among various rat strains using this PCR SA gene probe. Alleles at the SA locus strongly cosegregated with blood pressure (P = .0012) in a salt-fed F2 population derived from crossing Dahl S and Lewis rats. In contrast, a cosegregation analysis of blood pressure and SA alleles in salt-fed F2 rats derived from a Dahl S x Wistar-Kyoto cross gave a negative cosegregation result. It is concluded that in certain genetic backgrounds the SA gene (or a closely linked gene) can contribute a significant component of genetic hypertension.