Association of BMP4 rs17563 Polymorphism with Nonsyndromic Cleft Lip with or without Cleft Palate Risk: Literature Review and Comprehensive Meta-Analysis

Fetal Pediatr Pathol. 2021 Aug;40(4):305-319. doi: 10.1080/15513815.2019.1707916. Epub 2020 Jan 7.


Although published individual studies have reported associations between BMP4 rs17563 polymorphism and nonsyndromic cleft lip with or without cleft palate (NSCLP) risk, the results are conflicting. This meta-analysis was conducted to assess the association based on multiple studies. Methods: A comprehensive literature search up to October 1st, 2019 was performed using PubMed, Science Direct, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Results: Fourteen case-control studies with 2,058 NSCLP cases and 2,557 controls were selected. There was no significant association between BMP4 rs17563 polymorphism and risk of NSCLP overall. Subgroup analysis revealed that BMP4 rs17563 polymorphism was associated with NSCLP risk in Chinese and Brazilian populations. Conclusions: This meta-analysis suggests that BMP4 rs17563 polymorphism was not associated with NSCLP risk in overall population. However, BMP4 rs17563 polymorphism may be a risk factor for development of NSCLP in Chinese and Brazilians.

Keywords: Bone Morphogenetic Protein; Meta-Analysis; Non-syndromic Cleft Lip ± Palate; Polymorphism; Population.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Bone Morphogenetic Protein 4 / genetics
  • Case-Control Studies
  • China
  • Cleft Lip* / genetics
  • Cleft Palate* / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide


  • BMP4 protein, human
  • Bone Morphogenetic Protein 4