Anorectal atresia and variants at predicted regulatory sites in candidate genes.
Ann Hum Genet
; 77(1): 31-46, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23127126
ABSTRACT
Anorectal atresia is a serious birth defect of largely unknown etiology but candidate genes have been identified in animal studies and human syndromes. Because alterations in the activity of these genes might lead to anorectal atresia, we selected 71 common variants predicted to be in transcription factor binding sites, CpG windows, splice sites, and miRNA target sites of 25 candidate genes, and tested for their association with anorectal atresia. The study population comprised 150 anorectal atresia cases and 623 control infants without major malformations. Variants predicted to affect transcription factor binding, splicing, and DNA methylation in WNT3A, PCSK5, TCF4, MKKS, GLI2, HOXD12, and BMP4 were associated with anorectal atresia based on a nominal P value < 0.05. The GLI2 and BMP4 variants are reported to be moderately associated with gene expression changes (Spearman's rank correlation coefficients between -0.260 and 0.226). We did not find evidence for interaction between maternal pre-pregnancy obesity and variants in MKKS, a gene previously associated with obesity, on the risk of anorectal atresia. Our results for MKKS support previously suggested associations with anorectal malformations. Our findings suggest that more research is needed to determine whether altered GLI2 and BMP4 expression is important in anorectal atresia in humans.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anus Imperfurado
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Newborn
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article