alpha-Adducin 460Trp allele is associated with erythrocyte Na transport rate in North Sardinian primary hypertensives.
Erythrocyte membrane alterations mirror those of vascular smooth muscle and renal tubular cell membrane. The interaction between adducin and Na-K pump is the most likely biochemical mechanism responsible for the increased tubular Na reabsorption and hypertension in Milan hypertensive strain (MHS) rats. To substantiate this hypothesis in humans, we tested to see if alpha-adducin Gly460Trp genotype is associated with erythrocyte sodium transport rate in a new cohort of n=268 never-treated North Sardinian primary hypertensives. Plasma renin activity and blood pressure response to hydrochlorothiazide were also measured to evaluate the relationship between sodium transport rate and two intermediate phenotypes with a higher degree of genetic complexity. Na-K pump, Na-K-Cl cotransport, and Li-Na countertransport at V(max) were faster (P<0.0001), whereas intracellular Na concentration was lower (P<0.0001) in patients carrying one or two 460Trp alleles. Such behavior was mirrored by opposite changes of intracellular Na concentration. Plasma renin activity and blood pressure response to diuretic treatment, on the other hand, showed a weaker association with the sodium transport rate. In conclusion, our findings are consistent with the hypothesis that the Gly460Trp alpha-adducin polymorphism may affect renal Na handling through an alteration in ion transport across the cell membrane mirrored by erythrocytes. These results may also have clinical relevance because the Gly460Trp alpha-adducin polymorphism may explain, at least in part, the variability of blood pressure response to diuretics in primary hypertensive patients.
Glorioso
Nicola
N
Hypertension Center, University of Sassari Medical School, Sassari, Italy. glorioso@ssmain.uniss.it
Filigheddu
Fabiana
F
Cusi
Daniele
D
Troffa
Chiara
C
Conti
Milena
M
Natalizio
Marcella
M
Argiolas
Giuseppe
G
Barlassina
Cristina
C
Bianchi
Giuseppe
G
D000483:Alleles; D019943:Amino Acid Substitution; D000959:Antihypertensive Agents / Q000494:pharmacology; D001692:Biological Transport; D001794:Blood Pressure / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007558:Italy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D000099291:Adducins
D000959:Antihypertensive Agents; D002148:Calmodulin-Binding Proteins; D006852:Hydrochlorothiazide; D012083:Renin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D000099291:Adducins