Association of PRKCB Polymorphisms with Non-syndromic Orofacial Cleft among a Chinese Population

To investigate the association of PRKCB polymorphisms with non-syndromic orofacial cleft (NSOC) among a Chinese population.

A total of 2,724 patients with NSOC and 1,263 healthy controls of Han ethnicity were recruited. Clinical subtypes of NSOC were classified in detail, and 945 single nucleotide polymorphisms (SNPs) in the PRKCB gene were initially extracted from prior genome-wide association studies (GWAS) data. SNPs were selected based on minor allele frequency, Hardy-Weinberg equilibrium, call rate and linkage criteria, then genotyped using SNPscan. Statistical analyses included Hardy-Weinberg equilibrium testing, allelic/genotypic association analyses and linkage disequilibrium analysis. Functional annotation was conducted using RegulomeDB, 3DSNP and HaploReg databases.

Two PRKCB SNPs (rs198198 and rs174828) demonstrated significant or borderline associations with multiple NSOC subtypes. Notably, the A allele of rs198198 presented a risk for NSCL/P (P = 0.02) and NSCLP (P = 0.03) and C allele of rs174828 presented a risk for NSCL/P (P = 0.03) in allelic association analysis. Only rs174828 exhibited significant genotypic associations with NSOC (P = 0.02), NSCL/P (P = 0.02) and NSCPO (P 0.01). Functional annotation suggested both SNPs could modify transcription factor binding and enhancer activity.

These results demonstrate that rs198198 and rs174828 in PRKCB are associated with specific NSOC sub-phenotypes. Phenotype stratification and bioinformatics analyses highlight the role of PRKCB in NSOC susceptibility, highlighting the importance of non-canonical Wnt/Ca2±PKC signalling and emphasising the genetic heterogeneity within NSOC.