Association of rs8670 Polymorphism in the MSX1 Gene With Non-Syndromic Cleft Lip With or Without Cleft Palate in Malay Population

Objective: This study aimed to investigate the association between variants present in the MSX1 gene and the risk of developing non-syndromic cleft lip with or without cleft palate (NSCL +/- P) among individuals of Malay ethnicity in Malaysia. Materials and methods: This case-control study involved 89 patients with NSCL +/- P and 100 healthy control subjects. Polymerase chain reaction (PCR) was performed on both exon 1 and exon 2 of the MSX1 gene using four pairs of primers. The amplification products were then subjected to denaturing high-pressure liquid chromatography for initial screening, and the presence of a heteroduplex peak was validated using direct sequencing analysis to detect the single-nucleotide polymorphism. Results: Five previously known variations (c.-36G>A, p.Ala30Ala, p.Ala34Gly, p.Gly110Gly, and rs8670: C>T) were detected within the MSX1 gene in both NSCL +/- P patients and controls. A significant association was found between the rs8670: C>T variant and NSCL +/- P (p = 0.017; OR: 0.368; 95% CI: 0.152 - 0.893), with this particular single-nucleotide polymorphism present in 20% (20) among controls and 7.9% (7) of the NSCL +/- P cases. Conclusions: Our data showed a lower incidence of the rs8670: C>T polymorphism among NSCL +/- P cases compared to control in this Malay population. However, since this variant is located in the 3'UTR, it could potentially impact the stability of MSX1 mRNA.