Association of EPHA3 Gene Polymorphisms with Nonsyndromic Cleft Lip With or Without Cleft Palate

Aims: Nonsyndromic cleft lip with or without palate (NSCL/P) represents a complex condition caused by genetic and environmental factors. The aim of this study was to investigate the relationship between the EPHA3 polymorphisms and NSCL/P. Materials and Methods: To investigate the relationship between five EPHA3 single nucleotide polymorphisms (SNPs) and NSCL/P, we selected 180 affected patients and 167 normal controls from the Chinese Han Population. EPHA3 SNPs (rs7650466, rs1398197, rs17801309, rs1054750, and rs7632427) were genotyped using the SNaPshot technique and used to perform bioinformatic analyses to determine if any of them were potentially functional SNPs. Results: The rs7650466 T allele was associated with incidence of NSCL/P (OR, 0.211; 95% CI, 0.131-0.338; adjusted p=4.881x10(-10)) and cleft lip with or without palate (CL/P) (OR, 0.176; 95% CI, 0.104-0.297; adjusted p=3.617x10(-10)), as well as with protective and dominant effects in both conditions. The rs7650466 T allele could be associated with reduced risk of the malformation. In a bioinformatics analysis, we found potential matching sites (miR-1255a, miR-125a-3p, miR-143, and miR-552) for rs7650466 and preliminarily analyzed its potential function. Conclusions: Collectively, our data suggest that the EPHA3 rs7650466 polymorphism confers genetic risk for NSCL/P in the Chinese Han Population. Furthermore, rs7650466 is associated with CL/P incidence in stratified analysis, but not with cleft palate only.