This work was supported by a grant from the American Society of Pediatric Otolaryngology, a grant from the Doris Duke Charitable Foundation to Columbia University Medical Center (C.J.L., A.C.B.), and the Honduran Medical Institute. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations†
Article first published online: 2 JUL 2012
Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 122, Issue 9, pages 2082–2087, September 2012
How to Cite
Lennon, C. J., Birkeland, A. C., Nuñez, J. A. P., Su, G. H., Lanzano, P., Guzman, E., Celis, K., Eisig, S. B., Hoffman, D., Rendon, M. T. G., Ostos, H., Chung, W. K. and Haddad, J. (2012), Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations. The Laryngoscope, 122: 2082–2087. doi: 10.1002/lary.23394
- Issue published online: 23 AUG 2012
- Article first published online: 2 JUL 2012
- Manuscript Accepted: 28 MAR 2012
- Manuscript Revised: 14 MAR 2012
- Manuscript Received: 14 FEB 2012
- Cleft lip;
- cleft palate;
- candidate gene;
- Level of Evidence: 3b
Orofacial clefts are the most common craniofacial birth defects in humans, with the majority of orofacial clefts occurring as nonsyndromic cleft lip with or without cleft palate (NSCLP). We previously demonstrated associations between single-nucleotide polymorphisms (SNPs) in the IRF6 gene and NSCLP in the Honduran population. Here we investigated other candidate genes and chromosomal regions associated with NSCLP identified from genome-wide association studies (GWAS), including MAFB, ABCA4, 8q24, 9q22, 10q25, and 17q22 in two independent Hispanic populations.
Case-control and family-based association testing.
Honduran families with two or more members with NSCLP (multiplex) were identified. DNA was collected from affected and unaffected family members (488) and 99 gender-matched controls. NSCLP Colombian families were identified; DNA was collected from 26 proband-parent trios. All participants were genotyped for 17 SNPs in six chromosomal regions. Case-control association and family-based association testing (FBAT) analyses were conducted.
Seven SNPs demonstrated association in at least one model in the Honduran population. In the Colombian families, five SNPs demonstrated significance in FBAT when patients with isolated cleft palate (CP) were included; four overlapped with SNPs demonstrating significance in the Honduran population, two with the same allele. One SNP retained significance with CP excluded.
This study supports the previous GWAS findings and is the first to suggest a role for FOXE1, ABCA4, and MAFB in orofacial clefting in two separate Hispanic populations.