Different Roles Of MTHFR C677T And A1298C Polymorphisms In Nonsyndromic Orofacial Clefts

Objective The aim of this study was to investigate the associations of MTHFR C677T and A1298C with risks of Nonsyndromic orofacial clefts (NSOC).Methods DNA was extracted from 200 NSOC cases and 213 control subjects, which are frequency-matched to the cases on sex, age and residential region, were consecutively recruited from the Affiliated Stomatological Hospital of Nanjing Medical University and Nanjing Children's Hospital, from August 2008 to January 2010. Two MTHFR gene polymorphisms were applied by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Differences in the distributions of demographic characteristics and frequencies of genotypes and alleles of these two polymorphisms between the cases and controls were evaluated by Student's t-test (for continuous variables) or theχ2-test (for categorical variables). The odds ratios (OR) and 95% confidence internals (CI) were calculated by logistic regression analysis.Results For MTHFR C677T, there was no statistical difference between NSOC case group and control group (P>0.05). Children carrying TT and CT/TT genotype had an increased risk of NSOC. (OR = 1.84, 95% CI: 1.00, 3.37, OR=1.57, 95% CI: 1.02, 2.40 respectively). In the further stratified analysis by clefts subgroups, we found that MTHFR 677CT and 677TT contributed to elevated risk of cleft lip only (CLO) and cleft lip with or without cleft palate (CL/P),respectively For MTHFR A1298C, there was statistical difference between NSOC case group and control group (P<0.05). MTHFR 1298 AC and AC/CC genotype might contribute to a lower risk of NSOC (OR= 0.51, 95% CI: 0.32, 0.82, OR= 0.57, 95% CI: 0.36, 0.89, respectively). And MTHFR 1298AC and 1298AC/CC appeared to be protective factors of CL/P and cleft lip with cleft palate (CLP).Conclusion MTHFR C677T might be a risk factor of NOSC, while MTHFR A1298C might be a protective factor.