Common Mutations of the Methylenetetrahydrofolate Reductase (MTHFR) Gene in Non-Syndromic Cleft Lips and Palates Children in North-West of Iran

Introduction: Cleft lips and cleft palates are common congenital abnormalities in children. Various chromosomal loci have been suggested to be responsible the development of these abnormalities. The present study was carried out to investigate the association between the suspected genes (methylenetetrahydrofolate reductase [MTHFR] A۱۲۹۸C and C۶۷۷T) that might contribute into the etiology of these disorders through application of molecular methods.   Materials and Methods: This cross-sectional and explanatory study was carried out on a study population of ۶۵ affected children, ۱۳۰ respective parents and ۵۰ healthy individuals between ۲۰۰۹ and ۲۰۱۲ at Tabriz University of Medical Sciences, IR Iran. After DNA extraction, amplification refractory mutation system–polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphism (RFLP)-PCR were used respectively to investigate the C۶۷۷T and A۱۲۹۸C mutations for the MTHFR gene.   Results: There was a significant difference in the rates of the C۶۷۷T mutation when affected patients and their fathers were compared with the control group (odds ratio [OR]=۰.۴۴) (OR=۰.۶۴). However, there was no significant difference observed in the rate of this mutation between the patients’ mothers and the control group (OR=۱.۳۵). In addition, the abnormality rate was higher in patients with the A۱۲۹۸C mutation and their parents, when compared with the control group. This abnormality rate was higher for the affected children and their fathers in comparison with their mothers (Fathers, OR=۰.۲۶; Mothers, OR=۰.۶۵; Children, OR=۰.۵۵). No significant difference was seen in the rate of the polymorphism C۶۷۷T in its CC, when the affected children and their parents were compared with the control group. However, there was a significant difference in the A۱۲۹۸C mutation.   Conclusion:  An association was seen between the A۱۲۹۸C mutation and cleft lip and cleft palate abnormalities in Iran. However, there seems to be a stronger relationship between the C۶۷TT mutation and these abnormalities in other countries, which could be explained by racial differences. Moreover, this association was more notable between the affected children and their fathers than their mothers. The findings in this study may be helpful in future studies and screening programs.

کلیدواژه ها:

A۱۲۹۸C mutation ، Cleft lip ، Cleft palate ، C۶۷۷T mutation ، MTHFR