Association of common variants in ERBB4 with congenital left ventricular outflow tract obstruction defects

• DOI: 10.1002/bdra.20764
• Publication Date: 2011-02-02T18:28:32Z
• Authors: Kim L. McBride; Gloria A. Zender; Sara M. Fitzgeral...; Nikki J. Seagraves; Susan D. Fernbach; Gladys Zapata; Mark Lewin; Jeffrey A. Towbin; John W. Belmont
• Keywords: Left ventricular noncompaction; Ventricular outflow tract

Abstract BACKGROUND The left ventricular outflow tract (LVOT) defects aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic heart syndrome (HLHS) represent an embryologically related group congenital cardiovascular malformations. They are common cause substantial morbidity mortality. Prior evidence suggests a strong genetic component in their causation. METHODS We selected NRG1 , ERBB3 ERBB4 epidermal growth factor receptor (EGFR) signaling pathway as candidate genes for investigation association with LVOT based on importance this cardiac development phenotypes knockout mouse models. Single nucleotide polymorphism (SNP) genotyping was performed 343 affected case‐parent trios European ancestry. RESULTS identified specific haplotype intron 3 that positively associated combined phenotype ( p = 0.0005) each anatomic defect AVS, COA, HLHS separately. Mutation screening individuals failed to identify coding sequence or splice site change . RT‐PCR lymphoblastoid cells from subjects did not show altered variant ratios among those homozygous haplotype. CONCLUSION These results suggest is defects. Further replication will be required separate cohorts confirm consistency observed association. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.