The role of alpha-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study

The basic requirement for declaring an association study positive is that t he "hypertension-favoring" allele is more frequent in hypertensive cases th an in normotensive controls. However, both positive and negative associatio ns with hypertension have been found for the same polymorphism when studied in different populations. In the present study, we addressed the question of the possible cause(s) of this discrepancy among populations by using the alpha-adducin polymorphism as a paradigm. Four hundred ninety hypertensive s and 176 normotensives enrolled in Sassari, Italy, and 468 hypertensives a nd 181 normotensives enrolled in Milano, Italy, were genotyped for the alph a-adducin Gly460Trp polymorphism. The blood pressure response to 2 months o f hydrochlorothiazide therapy could be evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with and without the 460Trp alpha-adducin allel e, The alpha-adducin 460Trp allele was not significantly more frequent in h ypertensives in the Sassari population but was more frequent in hypertensiv es than in normotensives in Milano (P=0.019), Basal plasma renin activity-w as lower and blood pressure fall after diuretic therapy-more pronounced (P< 0.01) in hypertensives carrying at least one 460Trp allele than in Gly460Gl y homozygotes, irrespective of their membership in the Sassari or Milano co hort. The effect of alpha-adducin genotype in predicting basal plasma renin activity and blood pressure decrease with diuretic treatment is similar in Sassari and Milano,despite the lack of association of the cu adducin genot ype with hypertension in Sassari.