Polymorphisms of ATP-Binding Cassette, Sub-Family A, Member 4 (rs560426 and rs481931) and Non-Syndromic Cleft...

A number of genes are associated with the incidence of non-syndromic cleft lip/palate (NSCL/P). Studies have shown a significant association between polymorphisms of ATP-binding cassette, sub-family A, member 4 (ABCA4) with the risk of NSCL/P. The present meta-analysis assessed the association between ABCA4 polymorphisms (rs560426 and rs481931) and the NSCL/P risk by reviewing case-control studies.

Four databases (Scopus; Cochrane Library; Web of Science; and PubMed) were searched for articles published up to June 2020. The Review Manager 5.3 software was used to calculate the crude odds ratio (OR) and 95% confidence interval (CI). Both subgroup analyses for ethnicity and source of controls and a meta-regression related to publication year were conducted.

Of 94 retrieved studies, 12 were analyzed in this meta-analysis (2859 NSCL/P patients and 3792 controls for ABCA4 rs560426 polymorphism and 1333 NSCL/P patients and 1884 controls for ABCA4 rs481931 polymorphism). Overall, there was no significant association between both polymorphisms and the risk of NSCL/P. However, subgroup analysis demonstrated that there was a higher risk of NSCL/P for specific models: the allelic model (OR = 1.13; p = 0.03), the homozygote model (OR = 1.53; p = 0.04), and the recessive model (OR = 1.30; p = 0.03) in the Asian ethnicity for the rs560426 polymorphism.

The findings confirmed that the NSCL/P risk was significantly associated with the G allele and GG genotype of rs560426 polymorphism but not for rs481931 polymorphism. There were no associations between both polymorphisms (rs560426 and rs481931) and the NSCL/P risk in those of European descent and the mixed ethnicities.