Center for Human Genetics, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo.
Biol Res. 2009;42(4):461-8. Epub 2010 Jan 29.
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% 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.
人类 22q11 微缺失导致心脏血管型和面中部发育不全综合征和 DiGeorge 综合征。大多数患者共享一个共同的 3Mb 缺失，但临床表现非常异质。先天性心脏病在 50-80%的患者中存在，是发病率和死亡率的重要原因。表型的可变性表明存在修饰因子。血管内皮生长因子 A（VEGFA）基因的多态性与非综合征性先天性心脏病以及 22q11 微缺失患者心血管异常的存在有关。我们评估了 VEGFA 基因多态性 c.-2578C>A（rs699947）、c.-1154G>A（rs1570360）和 c.-634C>G（rs2010963）与智利患有 22q11 微缺失的患者的先天性心脏病的相关性。该研究使用病例对照和基于家庭的关联设计进行。我们评估了 122 名患有 22q11 微缺失且已知心脏和大血管解剖结构的患者及其父母。一半的患者患有先天性心脏病。我们没有通过任何一种分析方法获得关联的证据。我们的结果进一步证明了 22ql1 微缺失心血管表型的不完全外显率，但不支持 VEGFA 启动子多态性与智利患有这种综合征的患者先天性心脏病之间的关联。
