RESUMO
OBJECTIVE: This study aims to investigate genetic association between Non-syndromic Cleft lip with or without palate (NCLP) and 14 specific Single Nucleotide Polymorphism (SNPs) reported to be associated with NCLP from previous Genome Wide Association Studies (GWAS). DESIGN: A prospective case-control study. SETTING: Ministry of Health (MOH) Cleft and Craniofacial Clinic and Kuwait University. PATIENTS/PARTICIPANTS: One hundred sixty-four NCLP patients were recruited from MOH Cleft and Craniofacial clinic, and 491 controls from the Kuwait DNA bank established at Kuwait University. INTERVENTIONS: Total gDNA was extracted from whole blood withdrawn from patients and genotyped by real time PCR. Hardy-Weinberg Equilibrium was tested, and the set p value for significance (p < 0.05) was adjusted using the Benjamini - Hoochberg procedure to achieve 5% false discovery rate. MAIN OUTCOME MEASURES: Logistic regression multivariate analysis was used to test statistically significant differences between cases and controls. Genotyping both groups for the variants was determined through the allele discrimination software program. RESULTS: There was statistically significant difference between cases and controls in relation to two SNPs; LOC102724968 (rs13041247) (MAF cases/control = C (0.28/0.39) OR Homozygous = 1.30; 95% CI = 1.09-1.56, p = 0.0041) and PVT1 (rs987525) (MAF cases/control = A (0.41/0.27) OR heterozygous = 1.48; 95% CI =1.12-1.95, p = 0.0073), increasing the susceptibility to NCLP. CONCLUSIONS: Genetic variations are associated with the occurrence of oral clefts. Customized Next Generation Sequencing (NGS) panel to the Arab ethnicity is encouraged. In Addition, national preconception genetic carrier screening tests should expand to include common craniofacial anomalies.
