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Low expression VEGF haplotype increases the risk for tetralogy of Fallot: a family based association study

2005; BMJ; Volume: 42; Issue: 6 Linguagem: Inglês

10.1136/jmg.2004.026443

1468-6244

Diether Lambrechts,

Coronary Artery Anomalies

Congenital heart disease (CHD) presents a huge medical problem, as it affects between two and eight newborn children per 100 live births. 1 Risk factors include alcohol and drug consumption as well as genetic defects.However, chromosomal and single gene defects cause only a relatively minor proportion of cases and, thus, most CHD is considered to be multi-factorial in origin, with various genes interacting with each other or with environmental factors to determine disease liability. 2To date, none of the CHD genetic susceptibility factors have been discovered.Tetralogy of Fallot (TOF) is a common form of CHD, characterised by a subaortic ventricular septum defect (VSD), an overriding aorta, a right ventricular outflow tract obstruction, and right ventricular hypertrophy.TOF occurs in 4.21 of every 10 000 births and is the most common type of CHD with cyanosis after 1 year of life. 1 TOF may occur as part of the DiGeorge syndrome (DGS) which is caused by deletions of chromosome 22q11 and characterised by conotruncal cardiac, craniofacial, thymic, and parathyroid anomalies.However, in most cases (in 2.65 per 10 000 children) TOF occurs as an isolated defect.Mutations in the JAGGED1 or NKX2.5 genes have been found in only a few percentages of cases with isolated, non-syndromic TOF and thus, the genetic etiology in the large majority of these cases remains entirely unknown. 2 By using a multi-genetic approach, we recently discovered that VEGF is a modifier of DGS. 3 We therefore assessed here whether VEGF might be a modifier of the cardiac birth defects in subjects with isolated, non-syndromic TOF.