Backgroundα-adducin is a cytoskeletal protein involved with sodium-pump activity in the renal tubule. The α-adducin gene locus has been linked to hypertension and a polymorphism identified which is associated with hypertension; however, the role of the α-adducin gene locus in normal blood pressure regulation is not defined. We performed a combined linkage and association study in normotensive monozygotic (MZ) and dizygotic (DZ) twins and their parents to address this issue.MethodsWe studied 126 MZ and 70 DZ twin pairs and parents of DZ twins. Blood pressure values and responses to a cold pressor test were obtained. Cardiac dimensions were measured echocardiographically. Three microsatellites adjacent to the α-adducin gene were studied as well as the 460 Trp mutation in the α-adducin gene.ResultsWe obtained strong evidence for linkage (P< 0.001) between the α-adducin gene locus and systolic blood pressure. However, we were not able to associate the 460 Trp mutation with higher blood pressures, cold pressor responses or cardiac dimensions.ConclusionsThe α-adducin gene locus is relevant to blood pressure regulation in normal subjects. Failure to find an association between higher blood pressures and the 460 Trp mutation suggests that this mutation may become important only when hypertension is triggered, or that other variations in α-adducin are present which have not yet been discovered.