Examination of candidate genes at chromosome 7p22 in familial hyperaldosteronism type II

Jeske, YW, So, A, Kelemen, L, Bulmer, B, Gordon, RD, Duffy, D and Stowasser, M (2007). Examination of candidate genes at chromosome 7p22 in familial hyperaldosteronism type II. In: Hypertension: Proceedings of the High Blood Pressure Research Council of Australia 2006 Annual Scientific Meeting. 28th Annual Scientific Meeting of the High Blood Pressure Research Council of Australia, Brisbane, Australia, (1469-1469). 7-8 December 2006. doi:10.1161/HYPERTENSIONAHA.107.009421


Author Jeske, YW
So, A
Kelemen, L
Bulmer, B
Gordon, RD
Duffy, D
Stowasser, M
Title of paper Examination of candidate genes at chromosome 7p22 in familial hyperaldosteronism type II
Conference name 28th Annual Scientific Meeting of the High Blood Pressure Research Council of Australia
Conference location Brisbane, Australia
Conference dates 7-8 December 2006
Proceedings title Hypertension: Proceedings of the High Blood Pressure Research Council of Australia 2006 Annual Scientific Meeting   Check publisher's open access policy
Journal name Hypertension   Check publisher's open access policy
Place of Publication Baltimore, MD
Publisher Lippincott Williams & Wilkins for the American Heart Association
Publication Year 2007
DOI 10.1161/HYPERTENSIONAHA.107.009421
ISSN 0194-911X
Volume 49
Issue 6
Start page 1469
End page 1469
Total pages 1
Collection year 2008
Language eng
Abstract/Summary There are two types of familial hyperaldosteronism: FH-I and FH-II. FH-I is caused by a hybrid CYP11B1/CYP11B2 gene mutation. The genetic cause of FH-II, which is more common, is unknown. Adrenal hyperplasia and adenomas are features. We reported linkage of FH-II to a 4 Mb region on chr 7p22. Candidate genes at 7p22 involved in cell cycle control include retinoblastoma-associated Kruppel-associated box gene (RBaK), postmeiotic segregation increased 2 (PMS2) and guanine nucleotide-binding protein alpha-12 (GNA12). RBaK interacts with the retinoblastoma gene product to repress expression of genes activated by E2F transcription factors. PMS2 is involved in DNA mismatch repair and tumor predisposition. GNA12 is a transforming oncogene. We previously reported finding no causative mutations in RBaK and PMS2 coding regions. In the current study, (1) GNA12 exons and proximal promoter were examined in two affected (A1, A2) and two unaffected (U1, U2) subjects from FH-II family 1, and a normotensive control. No mutations were found. (2) The RBaK promoter was sequenced to -1300bp from the transcription start site. Two unreported single nucleotide polymorphisms (SNPs; C-1034G and T-1021C) were found in subjects A1, A2 but not in U1, U2 or the control. Additional subjects from 7p22-linked FH-II families 1, 2 and 3 and 68 controls were therefore genotyped. Results (see table) suggest that the –1034C/-1021T allele may be in linkage disequilibrium with the causative mutation in family 1. Its frequency among controls does not exclude it, since, based on recent data from the Framingham offspring study linking aldosterone/renin ratio to rising BP and chr 7p, it could indicate those predisposed to become hypertensive. Since this sequence alters the binding sites for several transcription factors in the RBaK promoter and may contribute to FH-II phenotype, these SNPs will be genotyped in additional FH-II subjects.
Subjects 321004 Endocrinology
730105 Endocrine organs and diseases (incl. diabetes)
EX
Keyword Peripheral Vascular Disease
Q-Index Code EX

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 18 Feb 2008, 17:18:06 EST