Nonmendelian inheritance of hypertension: Repetitive DNA sequences as candidates for genomic determinants

In contrast to secondary hypertension, primary or essential hypertension (E H) is a genetically determined disease. It is inherited in a nonmendelian m anner, i.e., not as a mono- or polygenic trait. This has been confirmed by the population genetic investigations studies of familial anamnesis and twi n pair studies carried out for more than 25 years. On the basis of the lite rature data and original findings, rearrangements of repetitive DNA sequenc es are suggested as candidates for EH determinants. If occurred in gametes, changes in the Organisation of these sequences are inherited. Since these changes are quantitative and, which is more important, dynamic, they will b e inherited in a noncanonic, nonmendelian manner. About 25% DNA is represen ted by clasters of repeated sequences. it was demonstrated that rearrangeme nts in these clasters, which have both chromosomal and telomeric location, can determine a pathology. However, it is unclear what molecular mechanism initiates these rearrangements. We have suggested that in EH they are trigg ered by retroposition. After insertion in the claster, a retroposon destabi lises it and probably triggers an increase or decrease in the number of cop ies. Superexpression of retrotransposon has been demonstrated in the genome of spontaneously hypertensive rats (SHR) which are recognised model of hum an EH. The authors have revealed a polymorphism in the location of ID retro poson copies revealed in the genome of SHR. Further investigation has shown that the distribution of ID repeats is coinherited with the arterial press ure level and other hemodynamic, morphological and biochemical characterist ics of spontaneous hypertension. If EH is regarded as pathology arising fro m rearrangements of repetitive DNA sequences, the specific phenotypic featu res of EH meet their genomic correlates.