Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations

Laryngoscope. 2012 Sep;122(9):2082-7. doi: 10.1002/lary.23394. Epub 2012 Jul 2.

Abstract

Objectives/hypothesis: 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.

Study design: Case-control and family-based association testing.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Alleles
  • Case-Control Studies
  • Cleft Lip / ethnology
  • Cleft Lip / genetics*
  • Cleft Lip / surgery
  • Cleft Palate / ethnology
  • Cleft Palate / genetics*
  • Cleft Palate / surgery
  • Colombia / ethnology
  • Confidence Intervals
  • Female
  • Forkhead Transcription Factors / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease / epidemiology*
  • Genome-Wide Association Study
  • Genotype
  • Hispanic or Latino / genetics
  • Honduras / ethnology
  • Humans
  • Incidence
  • Interferon Regulatory Factors / genetics
  • MafB Transcription Factor / genetics*
  • Male
  • Odds Ratio
  • Pedigree
  • Polymorphism, Single Nucleotide*
  • United States / epidemiology

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • FOXE1 protein, human
  • Forkhead Transcription Factors
  • Interferon Regulatory Factors
  • MAFB protein, human
  • MafB Transcription Factor