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- Title
Common Variation in ISL1 Confers Genetic Susceptibility for Human Congenital Heart Disease.
- Authors
Stevens, Kristen N.; Hakonarson, Hakon; Kim, Cecilia E.; Doevendans, Pieter A.; Koeleman, Bobby P. C.; Mital, Seema; Raue, Jennifer; Glessner, Joseph T.; Coles, John G.; Moreno, Victor; Granger, Anne; Gruber, Stephen B.; Gruber, Peter J.
- Abstract
Congenital heart disease (CHD) is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1) is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.
- Subjects
CONGENITAL heart disease; CASE studies; HEART abnormalities; TRANSCRIPTION factors; PROTEINS; GENETIC polymorphisms; DNA replication; DNA synthesis; ETIOLOGY of diseases
- Publication
PLoS ONE, 2010, Vol 5, Issue 5, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0010855