Abstract 534 Poster Session II, Sunday, 5/2 (poster 207)

Background: Familial hyperaldosteronism type-II (FH-II) is a dominantly inherited disease characterized by hypertension due to non-glucocorticoid suppressible autonomous hyperaldosteronism arising from either bilateral adrenal hyperplasia or aldosterone-producing adenomas. Diagnostic biochemical features of this disease include an elevated aldosterone and a suppressed plasma renin activity with an aldosterone/renin ratio (ARR) > 25 as well as failure of aldosterone suppression following 4 days of dexamethasone (0.25mg Q6H). Hypokalemia is not a consistent feature. Affected kindreds have been described in several countries although the largest collection published to date has been in Australia. Screening of affected kindreds has identified some normotensive patients who have had abnormally elevated ARR from their second decade of life. We aimed to use linkage analysis to identify candidate gene loci in several large Australian kindreds with FH-II.

Methods: Using an informative subset of a large 4 generation FH-II kindred, a genome wide screen was performed using polymorphic markers. Further refinement of potential loci was achieved by testing the full kindred and other kindreds with flanking polymorphic markers at 5 centimorgan (cM) intervals for a distance of 15-20 cM each side of markers yielding LOD scores greater than 1.0.

Results: The above approach has resulted in exclusion of more than 80% of the genome. Four candidate disease loci remained with LOD scores greater than 1.0. Attempts to refine the candidate loci have led to exclusion of a further two of these loci. Work is continuing on the remaining two loci.

Conclusion: FH-II is a dominantly inherited disorder resulting in low-renin hypertension and adrenal adenoma formation. Using linkage analysis, more than 80% of the genome has been excluded. Identification of the gene responsible for this rare disorder may provide further insight into genes responsible for low renin hypertension which accounts for 20% of essential hypertension.