Evaluating the Role of VAX1, MAFB, and NOG in Non-Syndromic Cleft Palate Only Among Japanese Individuals.

Abstract

Non-syndromic cleft palate only (NSCPO) is a distinct clinical and etiological entity within the spectrum of orofacial clefts. While genome-wide association studies (GWAS) have identified numerous risk loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P), the genetic architecture of NSCPO remains less understood, particularly in the Japanese population. This study aimed to investigate the association of three candidate genes, VAX1, MAFB, and NOG, with NSCPO risk. A case-control study was carried out involving 65 Japanese NSCPO patients and 119 ethnically matched healthy controls. Three single-nucleotide polymorphisms (SNPs), rs7078160 (VAX1), rs13041247 (MAFB), and rs227731 (NOG), were selected based on previous GWAS and minor allele frequency. Statistical associations were evaluated using chi-squared or Fisher's exact tests. The VAX1 rs7078160 polymorphism showed a significant association with NSCPO under a recessive model (OR = 2.10, 95% CI = 1.05-4.22, p = 0.034), with the AA genotype showing a higher risk. No significant associations were found for MAFB rs13041247 or NOG rs227731 (p > 0.05). Our findings identify VAX1 rs7078160 as a potential risk factor for NSCPO in the Japanese population. These results show the need for larger studies to further explain the molecular pathways of NSCPO.