The common non-synonymous variant G38S of the KCNE1-(minK)-gene is not associated to QT interval in Central European Caucasians: results from the KORA study.

AIMS The QT interval in the general population is a complex trait with 30-50% heritability. QT prolongation is associated with an increased risk of sudden death. A recent family-based study found an association between QT interval and the common non-synonymous Glycin 38 Serine variant (G38S, rs1805127) of the KCNE1 gene coding for the minK-potassium channel subunit. We intended to replicate this finding in a large population sample of central European Caucasian ancestry as part of our ongoing search for genetic variants predisposing to arrhythmias. METHODS AND RESULTS We studied 3966 unrelated individuals from the KORA S4 population-based study without atrial fibrillation, pacemaker implant, or pregnancy. Individuals were genotyped by MALDI-TOF mass spectrometry. We did not detect any significant association between the genotypes of the G38S variant and the QT interval in the entire population or in any gender. CONCLUSION Unlike the common Lysine 897 Threonine variant of KCNH2 (K897T, rs1805123) the G38S variant of KCNE1 does not appear to have a strong modifying effect on QT interval. However, we cannot rule out an effect of G38S on QT in other ethnic groups, under exercise or medications or on the risk for arrhythmias and sudden death.

[1]  G. Faggian,et al.  Failed Amplatzer Septal Occluder device implantation due to an embryonic septal remnant. , 2007, European heart journal.

[2]  Christian Gieger,et al.  A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization , 2006, Nature Genetics.

[3]  N. Sotoodehnia,et al.  Possible Association of the Human KCNE1 (minK) Gene and QT Interval in Healthy Subjects: Evidence from Association and Linkage Analyses in Israeli Families , 2005, Annals of human genetics.

[4]  Beverley Balkau,et al.  Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population , 2005, European Journal of Human Genetics.

[5]  C. Gieger,et al.  KORA-gen - Resource for Population Genetics, Controls and a Broad Spectrum of Disease Phenotypes , 2005 .

[6]  R. Holle,et al.  Common Variants in Myocardial Ion Channel Genes Modify the QT Interval in the General Population: Results From the KORA Study , 2005, Circulation research.

[7]  A. Busjahn,et al.  Single nucleotide polymorphism map of five long-QT genes , 2005, Journal of Molecular Medicine.

[8]  Michael J Ackerman,et al.  Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. , 2003, Mayo Clinic proceedings.

[9]  H. Huikuri,et al.  Association between HERG K897T polymorphism and QT interval in middle-aged Finnish women. , 2002, Journal of the American College of Cardiology.

[10]  H. Snieder,et al.  QT interval in twins , 2000, Journal of Human Hypertension.

[11]  H. Knoblauch,et al.  QT interval is linked to 2 long-QT syndrome loci in normal subjects. , 1999, Circulation.

[12]  F. Lehmann-Horn,et al.  Voltage-gated ion channels and hereditary disease. , 1999, Physiological reviews.

[13]  D. Kass,et al.  Sudden cardiac death in heart failure. The role of abnormal repolarization. , 1994, Circulation.

[14]  D. Levy,et al.  An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study) , 1992, The American journal of cardiology.

[15]  J. L. Willems,et al.  The diagnostic performance of computer programs for the interpretation of electrocardiograms. , 1992, The New England journal of medicine.

[16]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[17]  M. Näbauer Tuning repolarization in the heart: a multitude of potassium channels and regulatory pathways. , 2001, Circulation research.

[18]  M. Russell,et al.  Heritability of ECG measurements in adult male twins. , 1998, Journal of electrocardiology.

[19]  G. Tomaselli,et al.  Sudden Cardiac Death in Heart Failure , 1998 .