Microdeletion 22q11 in
humans causes velocardiofacial and DiGeorge
syndromes. Most
patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous.
Congenital heart disease is present in 50-80 percent of
patients and is a significant cause of
morbidity and
mortality. The
phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA
gene,
coding for the
vascular endothelial growth factor A, have been associated with non-syndromic
congenital heart disease, as well as with the presence of cardiovascular anomalies in
patients with microdeletion 22q11. We evaluated the
association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with
congenital heart disease in Chilean
patients with microdeletion 22q11. The study was performed using case-control and
family-based
association designs. We evaluated 122
patients with microdeletion 22q11 and known
anatomy of the
heart and great vessels, and their
parents. Half the
patients had
congenital heart disease. We obtained no evidence of
association by either
method of
analysis. Our results provide further evidence of the incomplete
penetrance of the cardiovascular
phenotype of microdeletion 22ql 1, but do not support
association between VEGFA promoter polymorphisms and the presence of
congenital heart disease in Chilean
patients with this
syndrome.