OR-12: No association between primary aldosteronism and two CYP11B2 polymorphisms in a well-characterized Australian sample

Abstract

Two aldosterone (aldo) synthase gene (CYP11B2) polymorphisms have been reported to be associated with undifferentiated hypertension (HT), low renin HT and HT due to primary aldosteronism (PAL); (i) a C-344T substitution at a steroidogenic factor-1 binding site in the promoter and (ii) a conversion involving transfer of intron 2 from 11β-hydroxylase (CYP11B1). However, other studies have reported no association or implicated the other allele. So far, reported studies examining these polymorphisms have been confined to European or Japanese hypertensive populations. Using similar laboratory and statistical methods, we compared frequencies of these polymorphisms in 107 predominantly white Caucasian Australian patients with PAL (confirmed by fludrocortisone suppression testing after screening using aldo/renin ratio), with those in 99 normotensive controls. No differences in frequency were found for either polymorphism, whether comparing controls to all with PAL or to those with aldo producing adenoma [n=18] or bilateral adrenal hyperplasia [n=71] (differentiated by adrenal venous sampling). The two polymorphisms were in linkage disequilibrium, as previously reported. Reported associations with HT in several different populations could be due to linkage disequilibrium of these alleles with important functional polymorphisms. The conflicting association data may be a result of the CYP11B2 variants being present on multiple different risk haplotypes. Alternatively, ethnic background might be an important determinant of allele distribution for these polymorphisms. Given the current study's sample size, a direct effect of these polymorphisms in a small subset of our patients is possible, but it excludes overall relative risks greater than 1.9-fold. (See Table 1)

Tbale 1

Nucleotide-344		CC	TC	TT	%C	%T
	PAL	24 (0.22)	48 (0.45)	35 (0.33)	0.449	0.551
	Controls	17 (0.17)	49 (0.50)	33 (0.33)	0.419	0.581
		χ2 = 0.955, P = 0.620			χ2 = 0.362, P = 0.522
Intron 2: Wild Type (W) or Conversion (C)		WW	WI	II	%W	%I
	PAL	34 (0.32)	54 (0.50)	19 (0.18)	0.570	0.430
	Controls	33 (0.33)	41 (0.42)	25 (0.25)	0.540	0.460
		χ2 = 2.305, P = 0.316			χ2 = 0.367, P = 0.553

Aldosterone Synthase, Association Study, Primary aldosteronism

© American Journal of Hypertension, Ltd. 2005