Parental transmission effects of the IRF6 polymorphisms among Non-Syndromic Cleft Lip with or without cleft palate in Kerala case parent trios

Objective: The purpose of this study was to evaluate the IRF6 gene polymorphisms in the etiology of the Non-syndromic Orofacial Cleft (NSOFC) population from Kerala.

Design: The study included a hundred case-parent triads of NSOFC from the Kerala Population. Genomic DNA was isolated from the trios. The polymorphisms rs2235371 and rs7552506 were genotyped using polymerase chain reaction (PCR) and the Sanger sequencing method. PLINK and haploview software were used for the statistical analysis.

Results: We found a substantial association of the rs2235371 (p-value = 0.0094, OR = 2.2) with NSOFC. The allelic TDT analysis 'A' allele of rs2235371 showed significant paternal transmission (p-value = 0.03, P_POO=0.506), whereas the 'C' allele of rs7552506 (p-value = 0.0094, P_POO=0.0527) showed an excess maternal transmission. The linkage disequilibrium (LD) values (D'= 0.83 and r² =0.033) between rs2235371 and rs7552506 discovered that these two SNPs are not in strong LD. Haplotype A-G exhibited a significantly reduced risk for oral clefts (p=0.035).

Conclusion: The current study revealed that polymorphism rs2235371 is associated with NSOFC. The rs2235371 appears to be significant with the trait in the paternal lineage but not when considering both lineages together. On the other hand, rs7552506 shows a significant association in the maternal lineage, with the pooled analysis approaching statistical significance. This study indicates that the IRF6 gene may be a risk factor for NSOFC in the Kerala population.