Send to

Choose Destination
Avicenna J Med Biotechnol. 2015 Apr-Jun;7(2):80-4.

Maternal Supplementary Folate Intake, Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and the Risk of Orofacial Cleft in Iranian Children.

Author information

Dentofacial Deformities Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Pediatric Department, Dental School, Semnan University of Medical Sciences, Semnan, Iran.
Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Orthodontic Department, Dental school, Semnan University of Medical Sciences, Semnan, Iran.



The purpose of this study was to describe the association of MTHFR gene single nucleotide polymorphisms (C677T and A1298C) and maternal supplementary folate intake with orofacial clefts in the Iranian population.


In this case-control study, peripheral venous blood was taken from 65 patients with orofacial clefts and 215 unaffected controls for DNA extraction and kept in EDTA for further analysis. The genotyping was carried out using Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) and gel electrophoresis. Data were analyzed using Chi square test and logistic regression tests.


Genotype frequencies of 677TT were reported to be 13.5 and 36.1% in controls and CL/P patients, respectively, which showed a significant difference compared to CC as reference (OR=4.118; 95% CI=1.997-8.492; p=0.001). Conversely, 1298CC with frequencies of 10.8 and 12.7% in controls and patients, respectively, showed no significant difference compared to AA (OR=2.359; 95% CI=0.792-7.023; p=0.123). Comparing patients whose mothers did not report the folate supplement intake during pregnancy, to controls, it was observed that lack of folate intake was a predisposing factor for having a child with oral clefts (OR=5/718, p=0.000).


Children carrying the 677TT variant of the MTHFR gene may have an increased risk of CL/P. In addition, the finding that the risk associated with this allele was obviously higher when the mothers didn't use folic acid, supports the hypothesis that folic acid may play a role in the etiology of CL/P.


Cleft lip; Cleft palate; Genes; Polymorphism


Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center