Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, São Paulo, Brazil.
BMC Med Genet. 2013 May 16;14:53. doi: 10.1186/1471-2350-14-53.
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common orofacial birth defect with a wide range prevalence among different populations. Previous association studies with populations from Europe and Asia have identified putative susceptibility markers for NSCL/P in fibroblast growth factor 12 (FGF12), vinculin (VCL), connexin 43 (CX43) and in a region close to the ventral anterior homeobox 1 (VAX1) gene. However, there have thus far been no studies of these markers in NSCL/P Brazilian patients, and as the genetic ancestry of the Brazilian population is highly varied, the predisposition to those disease markers can be different.
Herein we conducted a structured association study conditioned on the individual ancestry proportions to determine the role of 16 polymorphic markers within those genes in 300 patients with NSCL/P and 385 unaffected controls.
None of the alleles and genotypes showed association with NSCL/P, though there was a significant association of the haplotype formed by VAX1 rs10787760, rs6585429 and rs1871345 polymorphisms with NSCL/P that did not persist Bonferroni correction for multiple tests.
Our results are consistent with a lack of involvement of FGF12, VCL and CX43 variants with NSCL/P pathogenesis in Brazilian patients. Furthermore, the higher frequency of a haplotype of VAX1 with NSCL/P patients suggests a low penetrant gene for oral cleft, and warrants further studies.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是最常见的口面先天畸形，在不同人群中的患病率差异很大。先前在欧洲和亚洲人群中进行的关联研究已经在成纤维细胞生长因子 12（FGF12）、粘着斑蛋白（VCL）、连接蛋白 43（CX43）和靠近前腹侧同源盒 1（VAX1）基因的一个区域中鉴定出了 NSCL/P 的潜在易感标记物。然而，迄今为止，还没有关于这些标记物在巴西 NSCL/P 患者中的研究，而且由于巴西人群的遗传背景高度多样化，这些疾病标记物的易感性可能会有所不同。
在此，我们根据个体的祖先比例进行了一项结构化关联研究，以确定这些基因中的 16 个多态性标记物在 300 名 NSCL/P 患者和 385 名无病对照者中的作用。
没有一个等位基因和基因型与 NSCL/P 相关，但 VAX1 的 rs10787760、rs6585429 和 rs1871345 多态性形成的单倍型与 NSCL/P 显著相关，但在进行多次检验的 Bonferroni 校正后，这种关联并不显著。
我们的结果与巴西患者中 FGF12、VCL 和 CX43 变体与 NSCL/P 发病机制无关的结论一致。此外，VAX1 单倍型在 NSCL/P 患者中的较高频率提示存在低外显率的口腔裂基因，值得进一步研究。
