ABSTRACT
MTHFR C677T and A1298C* have been studied to be associated with nonsyndromic orofacial cleft (NS OFC) among different populations with conflicting results. However, NS OFC is divided into phenotypes such as unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), cleft lip only (CLO), and cleft palate only (CPO) that may have different genetic heterogeneity. Analyzing MTHFR C677T, MTHFR A1298C* and its interactions/haplotypes specifically among NS OFC phenotypes to examine the role of these polymorphisms as the risk factor of NS OFC and its phenotypes among Indonesian. This study was a case-control design using samples obtained from the venous blood of 522 subjects (295 NS OFC consisting of 81 UCLP, 57 BCLP, 49 CLO, 108 CPO, and 227 healthy controls). After DNA was extracted, the PCR-RFLPs method was performed. The Chi-Square test was used with the Kolmogorov Smirnov and Exact Fisher alternatives. T allele (OR=1,880, p=0,0001) and CT genotype (OR=2,724, p=0,0001) of MTHFR C677T and C* allele (OR=1,672, p=0,0001), AC* (OR=2,112, p=0,0001) and C*C* genotype (OR=10,418, p=0,005) of the MTHFR A1298C* generally can increase the risk of NS OFC, and specifically in NS OFC phenotypes, T allele (OR=2,316, p=0,0001) and CT genotype (OR=4,294, p=0,0001) of MTHFR C677T had the highest risk of NS CLO while C*C* genotype (OR=18,080, p=0,0001) of MTHFR A1298C* had the highest risk of NS CPO. For the interactions, CC* haplotype (OR= 4,579, p=0,0001) and TC* haplotype (OR=5,191, p=0,0001) had strengthening effects to increase the risk of NSUCLP. MTHFR C677T, MTHFR A1298C*, and its allelic interactions had such different genetic heterogeneity as the strong risk factors of NS OFC and its phenotypes among Indonesian.
