Potential genetic markers for nonsyndromic oral clefts in the Brazilian population: A systematic review and meta-analysis

• Published in: Birth defects research Vol. 110; no. 10; p. 827
• Main Authors: Assis Machado, Renato, de Toledo, Isabela Porto, Martelli-Júnior, Hercilio, Reis, Silvia Regina, Neves Silva Guerra, Eliete, Coletta, Ricardo D
• Format: Journal Article
• Language: English
• Published: United States 01.06.2018
• Subjects: Alleles; Bone Morphogenetic Protein 4 - genetics; Brazil - epidemiology; Cleft Lip - genetics; Cleft Palate - genetics; Gene Frequency - genetics; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genotype; Humans; Inheritance Patterns; Interferon Regulatory Factors - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Odds Ratio; Polymorphism, Single Nucleotide - genetics; Brazil; Brazil; meta-analysis; nonsyndromic oral cleft; susceptibility; systematic review; genetic marker
• ISSN: 2472-1727
• DOI: 10.1002/bdr2.1208

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.