The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study
1 Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark
2 Department of Biomedical Sciences, University of Stellenbosch, Cape Town, South Africa
3 Department of Internal Medicine, Roskilde Hospital, Roskilde, Denmark
4 Department of Bacteriology, Statens Serum Institut, Copenhagen, Denmark
5 Department of Medicine B, Rigshospitalet, Copenhagen, Denmark
Journal of Negative Results in BioMedicine 2011, 10:12 doi:10.1186/1477-5751-10-12Published: 3 October 2011
The gene family KCNE1-5, which encode modulating β-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic disease associated with an improper hypertrophic response.
The coding regions of KCNE1, KCNE2, KCNE3, KCNE4, and KCNE5 were examined, by direct DNA sequencing, in a cohort of 93 unrelated HCM probands and 188 blood donor controls.
Fifteen genetic variants, four previously unknown, were identified in the HCM probands. Eight variants were non-synonymous and one was located in the 3'UTR-region of KCNE4. No disease-causing mutations were found and no significant difference in the frequency of genetic variants was found between HCM probands and controls. Two variants of likely functional significance were found in controls only.
Mutations in KCNE genes are not a common cause of HCM and polymorphisms in these genes do not seem to be associated with a propensity to develop arrhythmia