Association of MSX1 Gene Variants with Nonsyndromic Cleft Lip and/or Palate in the Pakistani Population

Objectives: This study investigated the association of MSX1 gene variants rs3821949 and rs12532 with nonsyndromic cleft lip and/or palate (NSCL/P) in the Pakistani population. Design: Comparative cross-sectional study. Setting: Multicenter of CL/P malformation. Patients/Participants: Unrelated Non-Syndromic cleft Lip/Palate patients and healthy controls were enrolled. Methods: One hundred (n= 100) subjects with NSCL/P and n= 50 unrelated healthy controls were enrolled in a multicenter comparative cross-sectional study. A tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to analyze MSXI gene single nucleotide variants (SNVs). Results: Among 100 NSCL/P subjects, the majority were males (56%; male: female=1.27: 1). Most of the cases (74%) had cleft lip and palate (CLP) compared to isolated clefts. Genotyping of MSX1 gene variant rs3821949 showed an increased risk for NSCL/P in various genetic models (P<0.0001), and the A allele exhibited a more than 4-fold increased risk among cases (OR=4.22: 95% CI=2.16-8.22; P<0.0001). Our investigation found no significant difference between the rs12532 variation and NSCL/P. Conclusion: Our study findings suggest that MSX1 gene variants may increase predisposition to NSCL/P in the Pakistani population. Further studies comprising large samples are required to identify the genetic aetiology of NSCL/P among our people.