Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension

Kumar, Natasha N., Benjafield, Adam V., Lin, Ruby C. Y., Wang, William Y. S., Stowasser, Michael and Morris, Brian J. (2003) Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension. Journal of Hypertension, 21 7: 1331-1337. doi:10.1097/HJH.0b013e328332031a

Author Kumar, Natasha N.
Benjafield, Adam V.
Lin, Ruby C. Y.
Wang, William Y. S.
Stowasser, Michael
Morris, Brian J.
Title Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension
Journal name Journal of Hypertension   Check publisher's open access policy
ISSN 0263-6352
Publication date 2003-07
Sub-type Article (original research)
DOI 10.1097/HJH.0b013e328332031a
Volume 21
Issue 7
Start page 1331
End page 1337
Total pages 7
Place of publication Washington, U.S.
Publisher Lippincott Williams & Wilkins
Collection year 2003
Language eng
Subject C1
321003 Cardiology (incl. Cardiovascular Diseases)
730106 Cardiovascular system and diseases
1103 Clinical Sciences
110306 Endocrinology
Formatted abstract
Objective: The CYP11B2 locus is an important candidate region in essential hypertension (HT). We therefore investigated CYP11B2 polymorphisms T-344C, T4986C and A6547G for association with essential HT. This included haplotype analysis and measurement of plasma aldosterone levels.

Methods: The three single nucleotide polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis of genomic DNA from 146 HT and 291 normotensive (NT) white subjects of Anglo-Celtic descent, in whom parental blood pressure status was the same as the subjects'. Genotype and allele frequencies in HTs and NTs were compared by [chi]2 analysis. Linkage disequilibrium and haplotype frequencies were estimated by the program ‘snphap'. Phenotype–genotype relationships were tested using one-way analysis of variance.

Results: The T-344C variant was associated with HT ([chi]2 = 7.4, P = 0.0064). This association was confined to female HTs (P = 0.0061 for genotypes, P = 0.0013 for alleles). A strong association with HT was also seen for the A6547G variant (P = 0.0015), being greatest in females (P < 0.0001). No association was seen for the T4986C variant. Haplotype analysis of the three single nucleotide polymorphisms across eight different haplotype combinations showed a significant association with HT ([chi]2 = 24, seven degrees of freedom, P < 0.001). No significant tracking of plasma aldosterone with genotype was observed.

Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in females of the Anglo-Celtic population studied. This was reinforced by haplotype analysis.
Keyword Peripheral Vascular Disease
Case-control Study
Haplotype Analysis
Aldosterone Synthase
Restriction Fragment Length Polymorphism
Molecular Genetics
Left-ventricular Structure
Ambulatory Blood-pressure
Candidate Genes
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 47 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 01:36:49 EST