Linkage and association of PAX7 polymorphisms (rs742071, rs766325, and rs4920520) with the risk of non-syndromic cleft lip with/without cleft palate: A systematic review and meta-analysis

The studies have reported several additional non-syndromic cleft lip/palate (NSCL/P) susceptibility loci. This systematic review and meta-analysis aimed to evaluate the linkage and association of PAX7 polymorphisms with the NSCL/P risk. A comprehensive search was conducted in the PubMed, Cochrane Library, Web of Science, and Scopus databases until May 15, 2021. The association between PAX7 polymorphisms and NSCL/P susceptibility was analyzed by calculation of the odds ratios (ORs) and 95% confidence intervals (CIs), and the linkage was assessed by the allelic transmission disequilibrium test. Some articles included more than one study (reporting more than one polymorphism). Therefore, nine articles including 13 studies were entered into the meta-analysis. With regard to the association of rs742071 polymorphism with the risk of NSCL/P, the pooled OR was 1.33 for the allelic (P < 0.0001), 1.98 for the homozygous (P = 0.0007), 1.41 for the heterozygous (P = 0.0267), and 1.15 for the dominant (P = 0.2542) models. For the association of PAX7 rs766325 and rs4920520 polymorphisms with the risk of NSCL/P, the pooled OR was 0.96 (P = 0.5571) and 1.14 (P = 0.1020), respectively. In addition, the pooled allelic transmission disequilibrium test for s742071 and rs766325 polymorphisms did not show any allelic linkage between these polymorphisms and susceptibility to NSCL/P. The main results of the present systematic review and meta-analysis showed an association between PAX7 rs742071 polymorphism and NSCL/P susceptibility; but there was no linkage or association with rs766325 and rs4920520 polymorphisms.