Association of the MTHFR C677T polymorphism and fragile X syndrome in an Iranian population

ABSTRACT

Background & Objective: Fragile X syndrome is one of the most common causes of inherited mental retardation in males after Down syndrome. To date less attention was to study secondary genetic factor that may play role in fragile X neuropathology. In central nervous system, folic acid derivatives participate in different process such as neural development and function, synthesis of neurotransmitters and DNA methylation. This study aimed to assess the possible association of three common polymorphisms of folate pathway key enzymes, methylentetra hydrofolate reductase, MTHFR (C677T and A1298C), and methionine synthase reductase, MTRR (A66G), polymorphisms with the development of fragile X syndrome. Methods: Genetic polymorphisms were examined in a case-control study of 38 unrelated male patients and 60 age/sex matched unrelated controls using PCR-RFLP method. Allele frequencies and genotypes were calculated by chi-square test. Results: signifi cantly increased frequencies of the 677T allele and the 677CT genotype in patients were observed compared to control (p=0.010; OR=2.459 for T allele frequency; p=0.028; OR=2.608 for CT genotype frequency). The statistical analysis demonstrated the signifi cant correlation between C677T MTHFR polymorphism and fragile X syndrome in Iranian population (p=0.018). However, no signifi cant case-control differences were found for A1298C MTHFR and A66G MTRR polymorphisms. Conclusions: The association between C677T MTHFR polymorphism and fragile X syndrome has been demonstrated for the fi rst time in Iran population. This study may be important in better understanding of molecular pathology of fragile X syndrome. Further studies need to be undertaken to evaluate these preliminary results in other populations.