Abstract

The etiology of orofacial cleft as Non-syndromic cleft lips with or without palate (NSCL/P) are complex which including genetic and environmental factors. To investigate maternal polymorphism of MTHFR C677T, A1298C and MSX1as the risk factor of NSCL/P in Sasak Tribe, Lombok Indonesia. The study was a case control study involving 148 subjects from Sasak Tribe, consisting of 35 children with NSCL/P-mother pairs and 39 healthy children-mother pairs as controls. EDTA blood was drawn from all subjects. Molecular analyses of MTHFR C677T, A1298C and MSX1 polymorphisms were done using PCR-RFLP. The risk factors were analyzed statistically using OR and Chi square test. Children with at least one copy of the MTHFR 1298C allele had a higher risk of NSCL/P (p=0.036, OR 2.7, 95% CI (1.1-7.0)). Maternal polymorphisms MTHFR C677T and MSX1 were not found to be risk factors of NSCL/P (p>0.05). New sequence variation of c.469 + 12G>A was found near the splice site region of exon 1 MSX1 in an affected child. MTHFR A1298C polymorphism increases the risk of NSCL/P in Sasak Tribe, Lombok, Indonesia. A novel sequenceof MSX1 c.469 + 12G>A was found. Further study with higher sample size to fullfill minimum number of subjects for genetic study may found more new novel polymorphisms.