Baylor College of Medicine, Houston, Texas, USA.
Am J Med Genet A. 2010 Feb;152A(2):299-304. doi: 10.1002/ajmg.a.33230.
Spina bifida, a neural tube closure defect (NTD) involving the posterior portion of what will ultimately give rise to the spinal cord, is one of the most common and serious birth defects. The etiology of spina bifida is thought to be multi-factorial and involve multiple interacting genes and environmental factors. The causes of this congenital malformation remain largely unknown. However, several candidate genes for spina bifida have been identified in lower vertebrates, including the planar cell polarity (PCP) genes. We used data from a case-control study conducted in California to evaluate the association between variation within several key PCP genes and the risk of spina bifida. The PCP genes included in this study were the human homologs of the Xenopus genes Flamingo, Strabismus, Prickle, Dishevelled, and Scrib, two of the homologs of Xenopus Wnt genes, WNT5A and WNT11, and two of the homologs of Xenopus Frizzled, FZD3 and FZD6. None of the 172 SNPs that were evaluated were significantly associated with spina bifida in any racial/ethnic group after correction for multiple testing. However, several SNPs in the PRICKLE2 gene had unadjusted P-value <0.01. In conclusion, our results, though largely negative, suggest that the PRICKLE2 gene may potentially modify the risk of spina bifida and deserves further investigation.
脊柱裂是一种神经管闭合缺陷（NTD），涉及最终会形成脊髓的后部，是最常见和最严重的出生缺陷之一。脊柱裂的病因被认为是多因素的，涉及多个相互作用的基因和环境因素。这种先天性畸形的原因在很大程度上仍然未知。然而，已经在低等脊椎动物中确定了几个脊柱裂的候选基因，包括平面细胞极性（PCP）基因。我们使用在加利福尼亚州进行的病例对照研究的数据来评估几个关键的 PCP 基因内的变异与脊柱裂风险之间的关联。本研究中包括的 PCP 基因是人 Xenoapus 基因 Flamingo、Strabismus、Prickle、Dishevelled 和 Scrib 的同源物、两个 Xenoapus Wnt 基因的同源物 WNT5A 和 WNT11 以及两个 Xenoapus Frizzled 的同源物 FZD3 和 FZD6。在进行多次测试校正后，在任何种族/民族群体中，评估的 172 个 SNP 中没有一个与脊柱裂显著相关。然而，PRICKLE2 基因中的几个 SNP 未经调整的 P 值<0.01。总之，尽管我们的结果主要是阴性的，但表明 PRICKLE2 基因可能潜在地改变脊柱裂的风险，值得进一步研究。
