Polymorphic Variants of V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog B (rs13041247 and rs11696257) and Risk of Non-Syndromic Cleft Lip/Palate: Systematic Review and Meta-Analysis

Abstract

Background: Non-syndromic cleft lip/palate (NSCL/P) has an etiology, including both genetic and environmental factors. Herein, we evaluated the association of rs13041247 and rs11696257 v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) polymorphisms with the risk of NSCL/P in a meta-analysis. Methods: The PubMed/Medline, Scopus, Cochrane Library, Web of Science, and HuGE Navigator databases were systematically searched to retrieve relevant articles published up to January 2019. The Newcastle–Ottawa scale was applied for quality evaluation of retrieved articles. The 95% confidence interval (CI) and crude odds ratio (OR) were calculated for each study using the Review Manager 5.3 software to show the association between MAFB polymorphisms and risk of NSCL/P. The comprehensive meta-analysis 2.0 software was used to calculate the publication bias. In addition, sensitivity analysis was carried out to show the stability of results. Results: Of 102 articles retrieved from the databases, 10 articles were analyzed in this meta-analysis. Ten articles, including eleven studies reporting rs13041247 MAFB polymorphism, included 3082 NSCL/P patients and 4104 controls. Three studies that reported rs11696257 MAFB polymorphism involved 845 NSCL/P patients and 927 controls. The rs11696257 MAFB polymorphism was not associated with the risk of NSCL/P, but the CC and TC genotypes of rs13041247 polymorphism were associated with the risk of NSCL/P. Nevertheless, the C allele and CC and TC genotypes were associated with a significant decline in the risk of NSCL/P in population-based studies. Conclusions: The results of this meta-analysis demonstrated that the risk of NSCL/P was related to rs13041247 polymorphism, not rs11696257 MAFB polymorphism. Well-designed studies are required to assess the interaction of MAFB and other genes with environmental factors in different ethnic groups.

The Mafb cleft‐associated variant H131Q is not required for palatogenesis in the mouse

“…As Mafb de/del mice died shortly after birth, we hypothesized that these animals would present with a cleft of their secondary palate. This hypothesis was also supported by human genetic association studies demonstrating the contribution of the MAFB locus to the etiology of orofacial clefting 7,11‐16 . We performed serial coronal sections of e14.5 and e17.5 murine heads (Figure 2).…”

“…In humans, this same point mutation is associated with non‐syndromic cleft lip and palate 7 . Additional SNPs in or around the MAFB chromosomal region have been associated with orofacial clefting in a variety of populations, 7,11‐16 identifying this region, and potentially MAFB , as a genetic contributor to OFCs. This raises the question as to why the MAFB locus appears to contribute risk for OFC in human, yet complete loss of function of the mouse gene does not lead to a cleft lip and/or palate in this animal.…”

“…Multiple gene discovery approaches have been used including linkage analysis, 4 genomic rearrangements, candidate genes, 5 and more recently genome‐wide association studies (GWAS) and whole exome sequencing 6‐10 . One locus replicated in multiple independent studies in diverse ethnic populations is located on the chromosomal region 20q12, near or in MAF bZIP transcription factor B ( MAFB ) 7,11‐16 . Targeted sequencing of the single MAFB exon and conserved elements 3′ of MAFB identified a rare missense variant in a highly conserved histidine leading to a glutamine at position 131 (Figure 1A) which is predicted to alter the protein structure and function by Polyphen2 17 .…”

Evidence Mapping and Quality Analysis of Systematic Reviews on Various Aspects Related to Cleft Lip and Palate

“…These steps resulted in the inclusion of 18 more SRs. Altogether, 144 SRs and MAs [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , ...…”

Genetic Factors in Nonsyndromic Orofacial Clefts

“…95,96 Several GWAS in European and Asian populations identified the role of MAFB in NS CLP. 97,98 Different systematic review and meta-analyses confirmed that the MAFB gene SNP (rs13041247) is associated with NSCL/P risk in different population; however, this association is not significant in East Asian or Caucasian populations, 99,100 whereas, the SNPs rs17820943 and rs6072081 of MAFB found to be associated with NSCLP in an East Asian population. 101…”