Toggle Main Menu Toggle Search

Open Access padlockePrints

Measured haplotype analysis of the aldosterone synthase gene and heart size

Lookup NU author(s): Professor Bernard Keavney

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Gene-association studies of heart size and the aldosterone synthase (CYP11B2) gene have produced inconsistent results, possibly because of limitations in the sample size and/or the number and location of the polymorphisms. An analysis of six polymorphisms spanning 6 kb of the CYP11B2 gene in Caucasian British families revealed a limited number of haplotypes because of strong linkage disequilibrium over this small region. The genotype and haplotype information was used in an association study involving 955 members of 229 families phenotyped for echocardiographic measures of heart size. In a mixed effects linear modelling analysis, the G5937C polymorphism was associated with cardiac wall thickness (P=0.02), and the intron conversion and A4550C polymorphisms were associated with left ventricular cavity size (P=0.02 and 0.002, respectively). Measured haplotype analyses confirmed the association of alleles at the intron conversion and G5937C polymorphisms with cardiac wall thickness (P = 0.02), and alleles at the intron conversion polymorphism with left ventricular cavity size (P = 0.04). The polymorphisms contributed to 2.0-3.4% of the variability in these traits. In summary, genetic polymorphisms at the CYP11B2 gene make a small contribution to quantitative variation in echocardiographic measures of heart size. These results point to the importance of analysing the full extent of genetic variation that captures the haplotype structure of a locus in gene association studies.


Publication metadata

Author(s): Mayosi BM, Keavney B, Watkins H, Farrall M

Publication type: Article

Publication status: Published

Journal: European Journal of Human Genetics

Year: 2003

Volume: 11

Issue: 5

Pages: 395-401

ISSN (print): 1018-4813

ISSN (electronic): 1476-5438

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.ejhg.5200967

DOI: 10.1038/sj.ejhg.5200967

PubMed id: 12734545


Altmetrics

Altmetrics provided by Altmetric


Share