Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil.
Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Brasília, DF, Brazil.
Birth Defects Res. 2018 Jun 1;110(10):827-839. doi: 10.1002/bdr2.1208. Epub 2018 Feb 15.
Although various genes and genomic regions were described as of susceptibility for nonsyndromic oral clefts (NOC), recent reports have demonstrated significant interethnic variations in the genetic predisposition, a situation that affects the Brazilian population, one of the most admixed populations in the world. Therefore, the purpose of this review was to describe the available information on genetic risk markers for NOC in the Brazilian population.
A systematic search of the literature was performed using LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases, and studies that investigated genetic susceptibility markers for NOC in the Brazilian population were retrieved. Markers with enough statistical data were subjected to meta-analysis using random- or fixed-effects model with odds ratio (OR) and 95% confidence intervals (95% CI) as effect measures.
Forty-nine studies conducted since 1999 were found, and in these 114 markers were evaluated throughout case-control or family-based approaches. Most of the studies were conducted with patients affected by nonsyndromic cleft lip with or without cleft palate (NSCL ± P), and 79 markers (69.3%) were evaluated by a single study only. Meta-analysis was performed with nine markers, and the most promising results were obtained for IRF6 (rs642961), 8q24 (rs987525 and rs1530300) and MTHFR (rs1801133), which were associated with increased risk for NSCL ± P, and for BMP4 (rs17563) that showed a protective effect for NSCL ± P.
A large number of genetic markers distributed in several genes/loci was associated with NOC in the Brazilian population, but in general the original studies included limited number of samples and unsatisfactory protocols. The classical risk markers located in IRF6 and 8q24 showed promising results as well as rs1801133 in MTHFR and rs17563 in BMP4, and they should be validated in larger and multicenter studies taking in consideration the variations in the miscegenation of Brazilian population.
尽管已经有多种基因和基因组区域被描述为非综合征性口腔裂（NOC）的易感基因，但最近的报告表明，遗传易感性在不同种族之间存在显著差异，这种情况也影响了巴西人口，巴西是世界上人口混合最多的国家之一。因此，本综述的目的是描述巴西人群中 NOC 的遗传风险标记物的现有信息。
使用 LILACS、LIVIVO、PubMed、Scopus 和 Web of Science 数据库进行系统的文献检索，并检索了研究巴西人群 NOC 遗传易感性标记物的研究。对具有足够统计数据的标记物进行荟萃分析，使用随机或固定效应模型，以比值比（OR）和 95%置信区间（95%CI）作为效应测量。
共发现 1999 年以来进行的 49 项研究，其中通过病例对照或家系研究评估了 114 个标记物。大多数研究都是针对非综合征性唇裂伴或不伴腭裂（NSCL±P）患者进行的，其中 79 个标记物（69.3%）仅由一项研究进行了评估。对 9 个标记物进行了荟萃分析，IRF6（rs642961）、8q24（rs987525 和 rs1530300）和 MTHFR（rs1801133）的结果最有希望，它们与 NSCL±P 的风险增加相关，而 BMP4（rs17563）则对 NSCL±P 有保护作用。
大量分布在几个基因/基因座的遗传标记物与巴西人群的 NOC 相关，但总体而言，原始研究的样本数量有限，方案也不尽人意。IRF6 和 8q24 中的经典风险标记物显示出有希望的结果，MTHFR 中的 rs1801133 和 BMP4 中的 rs17563 也是如此，这些标记物应该在更大的、多中心研究中进行验证，同时考虑到巴西人口混血的变化。
