POLYMORPHISM OF GAMMA-ADDUCIN GENE IN GENETIC-HYPERTENSION AND MAPPING OF THE GENE TO RAT CHROMOSOME 1Q55

Adducin (ADD) is a heterodimeric protein involved in cellular signal t ransduction. A mutation in the alpha subunit affects ion transport and blood pressure in primary hypertension of Milan rats (MHS) and humans . In rats this effect is modulated by another mutation in the beta sub unit. The recently described gamma subunit is a new member of the ADD family that should take the place of beta subunit in cells and tissues expressing alpha but not beta-Add. A missense mutation (Q(572)K) has been found in the gamma subunit of the Milan rats. Nineteen normotensi ve and five hypertensive inbred rat strains were genotyped for the pol ymorphisms in alpha, beta and gamma-Add genes. A disequilibrium was ev ident in the distribution of MHS-like Add genotype, being more frequen t between the hypertensive than the normotensive strains (Chi-Square=1 3.03, p=0.0003). In kidney, brain, spleen, liver and heart a cDNA diff ering from gamma subunit by an in-frame insertion of 96 nucleotides, w as found by PCR amplification and confirmed by RNase protection analys is. The rat gamma-Add gene was localized to chromosome 1q55 by fluores cence in situ hybridization. (C) 1997 Academic Press.