School of Dentistry, University of Texas Health Science Center at Houston, DBB-202, 6516 MD Anderson Blvd., Houston, TX 77030-3402, USA.
J Dent Res. 2012 May;91(5):473-8. doi: 10.1177/0022034512440578. Epub 2012 Feb 27.
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.
我们之前已经在美国人群中发现了 AXIN2 与口腔裂的关联。在这里，我们扩展了研究，以探索 682 个来自多个群体的腭裂家庭的 11 个 AXIN2 标记物的关联。通过基于家庭的关联测试，我们对每个 AXIN2 标记物的等位基因与裂隙进行了传递扭曲测试。我们观察到 SNP rs7224837 与所有合并人群的裂隙（p = 0.001）以及 SNP rs3923086 与亚洲人群的唇腭裂有关（p = 0.004）。我们在美国的另外 528 个腭裂家庭中证实了我们的关联发现（p < 0.009）。我们测试了 AXIN2 与其他腭裂易感基因座之间的基因-基因相互作用。我们评估并检测了在小鼠腭发育过程中 Axin2 mRNA 和蛋白的表达。此外，我们还观察到 Axin2 与 Irf6 蛋白的共定位，特别是在上皮中。我们的结果继续支持 AXIN2 在人类裂隙发生中的作用。应进行更多研究以增进我们对将 AXIN2 与口腔裂联系起来的生物学机制的理解。
