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Annals of Clinical & Laboratory Science 39:241-250 (2009)
© 2009 Association of Clinical Scientists

Heritability of Erythrocyte Sodium Permeability: A Possible Genetic Marker for Hypertension

Jong Y. Lee1,2,3, Ronald J. Prineas1,3 and John W. Eaton2
1 Department of Medicine, 2 Department of Laboratory Medicine and Pathology, and 3 Division of Epidemiology, University of Minnesota, Minneapolis, Minnesota

Address correspondence to John W. Eaton, M.D., Ph.D., Baxter Bldg. II, Suite 210, 580 South Preston St., Univ. of Louisville, Louisville, KY 40202, USA; tel 502 852 1075; fax 502 852 3661; e-mail eatonredox{at}aol.com.

Individuals genetically susceptible to hypertension may have preexisting membrane defects influencing cell sodium permeability. Fourteen Minnesotan families of Northern European descent were selected as having one or both progenitors with either high (HP) or low (LP) erythrocyte sodium permeability. We earlier found that over one-half of the 22Na+ influx into HP erythrocytes can be inhibited by micromolar amounts of furosemide, which has no apparent effect on LP erythrocytes. In these families, we find a significant midpoint parent/offspring correlation in the furosemide-sensitive component of erythrocyte 22Na+ flux rates (p <0.001). The relationship between parents and children in this metric trait is most consistent with a single locus, 2-allele system with variable expression, which suggests that enhanced furosemide-sensitive 22Na+ influx may be inherited as an autosomal recessive trait. Individuals with HP erythrocytes tend to have increased blood pressure and/or a family history of hypertension. The results were confirmed in these family samples with HP and LP 22Na+ influx (mmol/L RBC/hr): 0.404 ± 0.03 vs 0.232 ± 0.01 (p < 0.001); systolic blood pressure (mm Hg): 136 ± 4 vs 108 ± 4 (p < 0.001); and diastolic blood pressure (mm Hg): 89 ± 2 vs 69 ± 2 (p <0.001). These results may help to identify inherited factors involved in salt sensitive hypertension.

Keywords: erythrocyte sodium permeability, diuretics, ion transport, blood pressure, genetic linkage






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