D011: The association of β-T594M variant in the amiloride sensitive sodium channel with end stage renal disease

We have previously reported the identification of a variant (T594M) in the β-subunit of the amiloride-sensitive sodium channel that occurs exclusively in the African American population (Su et al., 1996, J. Am. Soc. Nephrol., 7:2543–2549). Lymphocytes from individuals with this mutant channel show increased sodium conductance in response to cAMP and loss of protein kinase C inhibition (Cui et al., 1997, PNAS 94:9962–6). Association of the β-T594M polymorphism with hypertension has been reported in blacks in London (Baker et al., 1998, Lancet 9:1388–92). We screened 168 normotensive African American subjects and 844 hypertensive African American patients for the β-T594M variant. In contrast to the study by Baker et al., we did not detect any significant difference in the allele frequency between the hypertensive and normotensive groups (0.036 and 0.037 respectively). However, the allele frequency in 205 patients with end stage renal disease (ESRD) was found to be higher (0.053) than the allele frequency in either the 168 normotensives or the 844 hypertensives on whom we had renal function data (p < 0.01). The higher allele frequency in ESRD was the same in patients with or without diabetes mellitus. Our results suggest that the β-T594M variant may be associated with ESRD in African Americans.