Family-Based Study of the BMP2 RS235768 Variant in Cleft Lip and Palate

This study aimed to determine the frequency of minor anomalies and the rs235768 BMP2 polymorphism in individuals with cleft lip and palate (CL/P), their parents, and controls. The study included 121 individuals with CL/P, 121 parents, and 727 controls. Minor anomalies were recorded in the parents, and DNA was extracted from the saliva of patients with CL/P and their parents. The polymorphic region was amplified by PCR, sequenced using the Sanger method, and analyzed using FinchTV. In the control group, the variant was analyzed using next-generation sequencing–whole exome sequencing (NGS-WES). Allele and genotype frequencies were calculated for each group, and crude and adjusted odds ratios (ORs) were estimated to evaluate the associations. For minor anomalies, a bivariate analysis was performed using the Chi-square or Fisher’s exact test. For allele and phenotype frequencies, Chi-square, McNemar, and Pearson tests were applied. The most frequent minor anomalies in the parents were nostril and ear asymmetries. The thymine/thymine (TT) genotype was the most common, whereas adenine/adenine (AA) was the least frequent in all groups. Compared with parents, the AA genotype increased the likelihood of CL/P by 1.73-fold ( P =0.03). Comparing parents and controls, the adenine/thymine (AT) genotype increased the risk 1.5-fold ( P =0.024), while the TT genotype was associated with reduced susceptibility ( P =0.024). In conclusion, the AA genotype was associated with an increased risk of CL/P in patients. The AT genotype was also associated with a higher risk in parents than in controls. In contrast, the TT genotype, observed in both controls and parents, was associated with a reduced likelihood of developing the malformation.