1. Association of AXIN2 with non-syndromic oral clefts in multiple populations.
- Author
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Letra A, Bjork B, Cooper ME, Szabo-Rogers H, Deleyiannis FW, Field LL, Czeizel AE, Ma L, Garlet GP, Poletta FA, Mereb JC, Lopez-Camelo JS, Castilla EE, Orioli IM, Wendell S, Blanton SH, Liu K, Hecht JT, Marazita ML, Vieira AR, and Silva RM
- Subjects
- Animals, Asian People genetics, Axin Protein biosynthesis, China, Epistasis, Genetic, Europe, Gene Frequency, Genome-Wide Association Study, Humans, India, Interferon Regulatory Factors biosynthesis, Interferon Regulatory Factors genetics, Latin America, Linkage Disequilibrium, Mice, Palate, Hard embryology, Polymorphism, Single Nucleotide, Saliva chemistry, Turkey, United States, White People genetics, Axin Protein genetics, Cleft Lip genetics, Cleft Palate genetics
- Abstract
We have previously shown the association of AXIN2 with oral clefts in a US population. Here, we expanded our study to explore the association of 11 AXIN2 markers in 682 cleft families from multiple populations. Alleles for each AXIN2 marker were tested for transmission distortion with clefts by means of the Family-based Association Test. We observed an association with SNP rs7224837 and all clefts in the combined populations (p = 0.001), and with SNP rs3923086 and cleft lip and palate in Asian populations (p = 0.004). We confirmed our association findings in an additional 528 cleft families from the United States (p < 0.009). We tested for gene-gene interaction between AXIN2 and additional cleft susceptibility loci. We assessed and detected Axin2 mRNA and protein expression during murine palatogenesis. In addition, we also observed co-localization of Axin2 with Irf6 proteins, particularly in the epithelium. Our results continue to support a role for AXIN2 in the etiology of human clefting. Additional studies should be performed to improve our understanding of the biological mechanisms linking AXIN2 to oral clefts.
- Published
- 2012
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