No Association of MTHFR677CT and Cleft Lip/Palate in Karaikal, India

INTRODUCTION: Methylenetetrahydrofolate reductase (encoded by MTHFR gene) catalyzes conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is a co-substrate for methylation of homocysteine to methionine. This activity makes MTHFR critically important in the folate metabolic pathway. 5-methyltetrahydrofolate is the major circulating form of folate that is utilized in many biochemical pathways.

Various congenital anomalies, including neural tube defects and orofacial clefts (OFC), and some diseases have been found associated with 677CT and 1298AC polymorphisms of MTHFR.

OBJECTIVE: According to the Amrita Institute of Medical Sciences in Cochin India, 35,000 children with OFC are born in India every year. Objective of this study was to determine, whether an association between MTHFR677CT polymorphism and OFC exists in the population of Karaikal, India.

METHODS: Case-control design was used. The sample of cases consisted of 139 individuals affected with nonsyndromic cleft lip with or without cleft palate (NCLP). The control sample had 115 individuals. DNA was isolated from dry blood spots on filter paper. MTHFR677CT genotypes were established using PCR amplification and SNCP detection on polyacrylamide gels after electrophoresis.

RESULTS: Proportions of genotypes were 84.2% CC, 13.7% CT, and 2.19% TT in cases and 82.2% CC, 17.4% CT, and no TT in controls . The C allele frequency was 0.910 for cases and 0.913 for controls, while the T allele frequency was 0.09 for cases and 0.087 for controls. The differences between case and control samples were not statistically significant.

CONCLUSIONS: Results of this pilot study indicated no association of MTHFR677CT polymorphism with NCLP in this population. Evaluation of a larger sample will be needed to draw a more definitive conclusion about a role of T allele of the MTHFR677CT in etiology of NCLP in Karaikal.

ACKNOWLEDGEMENT: The fieldwork was supported by Rotaplast Intl., Inc.