Novel predictor of symptoms in LQTS

Novel predictor of symptoms in LQTS

Novel predictor of symptoms in LQTS: Variation in the penetrance of long QT syndrome is always a problem while trying to predict the clinical course in family members of patients. Lia Crotti, Maria Cristina Monti, Roberto Insolia, Anna Peljto, Althea Goosen, Paul A Brink, David A Greenberg, Peter J Schwartz and Alfred L George Jr [1] after studying 500 subjects of whom 205 were mutation carriers found that severity of symptoms as well as the QT interval could be correlated with genetic variations in nitric oxide synthase adaptor protein (NOS1AP). NOS1AP acts as a genetic modifier in phenotypic expression. Earlier large population studies also had documented that the NOS1AP was associated with a small increase in QT interval and increased risk of death in the general population. A study by Dan E Arking, Arne Pfeufer, Wendy Post, W H Linda Kao, Christopher Newton-Cheh, Morna Ikeda, Kristen West, Carl Kashuk, Mahmut Akyol, Siegfried Perz, Shapour Jalilzadeh, Thomas Illig, Christian Gieger, Chao-Yu Guo, Martin G Larson, H Erich Wichmann, Eduardo Marbán, Christopher J O’Donnell, Joel N Hirschhorn, Stefan Kääb, Peter M Spooner, Thomas Meitinger and Aravinda Chakravarti showed that about 60% of people of European ancestry carry at least one minor allele of the NOS1AP genetic variant which would explain up to 1.5% of QT interval variation [2].

Future studies will address the role of NOS1AP as a genetic modifier in other inherited arrhythmic disorders.

References

1. Lia Crotti, Maria Cristina Monti, Roberto Insolia, Anna Peljto, Althea Goosen, Paul A Brink, David A Greenberg, Peter J Schwartz, Alfred L George Jr. NOS1AP is a genetic modifier of the long-QT syndrome. Circulation. 2009 Oct 27;120(17):1657-63.
2. Dan E Arking, Arne Pfeufer, Wendy Post, W H Linda Kao, Christopher Newton-Cheh, Morna Ikeda, Kristen West, Carl Kashuk, Mahmut Akyol, Siegfried Perz, Shapour Jalilzadeh, Thomas Illig, Christian Gieger, Chao-Yu Guo, Martin G Larson, H Erich Wichmann, Eduardo Marbán, Christopher J O’Donnell, Joel N Hirschhorn, Stefan Kääb, Peter M Spooner, Thomas Meitinger, Aravinda Chakravarti. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet. 2006 Jun;38(6):644-51.