Targeted Resequencing Identifies Novel MAFB Variants Associated With Nonsyndromic Cleft Lip With or Without Cleft Palate

ObjectivesNonsyndromic cleft lip with or without palate (NSCL/P) is one of the most prevalent congenital orofacial defects. It arises from a combination of genetic and environmental factors. This study aims to identify new risk loci around the musculoaponeurotic fibrosarcoma oncogene family, protein B (<i>MAFB</i>) gene in NSCL/P patients from the Western Han Chinese population.DesignA targeted region sequencing approach was employed to examine the <i>MAFB</i> gene in 159 NSCL/P cases. We conducted both single-variant association and gene-based burden analyses.SettingThe study was conducted in a stomatological hospital.Patients, participantsOne hundred and fifty-nine NSCL/P cases were analyzed.InterventionsBlood samples were collected.Main outcome measuresTo explore the association analysis between variants at <i>MAFB</i> and NSCL/P in Western Han Chinese population.ResultsWe identified a cluster of significant common variants near the 3' end of <i>MAFB</i>. Notably, rs6029223 showed significantly associated with NSCL/P (<i>P </i>= 3.82E-09, odds ration [OR]<i> </i>=<i> </i>0.29, 95% confidence interval [CI]: 0.18-0.46), nonsyndromic cleft lip and palate (NSCLP) (<i>P </i>= 5.31E-08, OR<i> </i>=<i> </i>0.25, 95% CI: 0.14-0.44) and nonsyndromic cleft lip only (NSCLO) (<i>P </i>= 1.3E-04, OR<i> </i>=<i> </i>0.34, 95%CI: 0.19-0.62). In Addition, rs79836852 and rs200392238 were significantly associated with both NSCL/P and NSCLP.ConclusionsOur study revealed that single nucleotide polymorphisms near the 3' end of the <i>MAFB</i> gene are risk factors for NSCL/P and NSCLP in the Western Han Chinese population. Our findings reinforce the notion that <i>MAFB</i> is a susceptibility gene for NSCL/P.