Deak Kristen L, Dickerson Margaret E, Linney Elwood, Enterline David S, George Timothy M, Melvin Elizabeth C, Graham Felicia L, Siegel Deborah G, Hammock Preston, Mehltretter Lorraine, Bassuk Alexander G, Kessler John A, Gilbert John R, Speer Marcy C
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Birth Defects Res A Clin Mol Teratol. 2005 Nov;73(11):868-75. doi: 10.1002/bdra.20183.
Vitamin A (retinol), in the form of retinoic acid (RA), is essential for normal development of the human embryo. Studies in the mouse and zebrafish have shown that retinol is metabolized in the developing spinal cord and must be maintained in a precise balance along the anteroposterior axis. Both excess and deficiency of RA can affect morphogenesis, including failures of neural tube closure.
We chose to investigate 5 genes involved in the metabolism or synthesis of RA, ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2, for their role in the development of human neural tube defects, such as spina bifida.
An association analysis using both allelic and genotypic single-locus tests revealed a significant association between the risk for spina bifida and 3 polymorphisms in the gene ALDH1A2; however, we found no evidence of a significant multilocus association.
These results may suggest that polymorphisms in ALDH1A2 may influence the risk for lumbosacral myelomeningocele in humans.
视黄酸（RA）形式的维生素A（视黄醇）对人类胚胎的正常发育至关重要。在小鼠和斑马鱼中的研究表明，视黄醇在发育中的脊髓中代谢，并且必须沿前后轴保持精确的平衡。RA过多或过少都会影响形态发生，包括神经管闭合失败。
我们选择研究参与RA代谢或合成的5个基因，即醛脱氢酶1家族成员A2（ALDH1A2）、细胞色素P450 26家族成员A1（CYP26A1）、细胞色素P450 26家族成员B1（CYP26B1）、细胞视黄酸结合蛋白1（CRABP1）和细胞视黄酸结合蛋白2（CRABP2），以探究它们在人类神经管缺陷（如脊柱裂）发生发展中的作用。
使用等位基因和基因型单基因座检测进行的关联分析显示，脊柱裂风险与ALDH1A2基因中的3种多态性之间存在显著关联；然而，我们没有发现显著多位点关联的证据。
这些结果可能表明，ALDH1A2基因多态性可能会影响人类腰骶部脊髓脊膜膨出的风险。
