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677→CT mutation on the methylenetetrahydrofolate reductase gene is not a risk factor for neural tube defects in Turkey
  1. Hacettepe University
  2. Department of Pediatrics
  3. Clinical Genetics Unit
  4. 06100 Samanpazari
  5. Ankara
  6. Turkey

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    Editor—Recent studies have shown that periconceptual folic acid supplementation reduces a woman’s risk of having a baby with neural tube defects (NTD). Mothers of infants with NTD have increased homocysteine activities. People with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme is caused by a common mutation (677→CT) in the MTHFR gene. In different populations the 677→CT mutation has been implicated in susceptibility to NTD.1 We studied the 677→CT mutation as a risk factor for spine bifida in a group of Turkish patients with NTD, and in their parents.

    Blood for mutation analysis was obtained after written informed consent from cases with NTDs, and their parents. The study protocol was approved by the ethics committee of Hacettepe University Faculty of Medicine. The study population comprised 49 subjects with NTDs, 40 mothers, and 33 fathers. The control group consisted of 93 healthy adults of Turkish origin.

    We genotyped blood samples using the polymerase chain reaction and allele specific restriction digestion, according to the method described by Frosst et al.2 Our data showed no evidence for an association between the 677→Thomozygote genotype and the occurrence of NTD (table1). The homozygote TT prevalences were, respectively, 8.2% for NTD cases, and 7.5% for controls (OR 0.916, 95% CI 0.255–3.294; p=0.893). The TT genotype was more rare among the parents (12.3%, n=9) of NTD cases than among the control group (OR 1.728, 95% CIl 0.611–4.885; p=0.298).

    The prevalence of the 677→T allele differs among different populations. It has been noticed that the prevalence is relatively low in controls in those countries where the MTHFR polymorphism has been implicated in susceptibility to NTD.3 Although the prevalence of the 677→T allele in the Turkish control group (0.28) is very close to that of Dutch and Irish populations,1 where the MTHFR mutation has been implicated in a predisposition to NTD, we found no evidence for the association between the MTHFR mutation and NTD in the Turkish population studied.

    It has been suggested that 677→CT mutation might not be responsible for a large percentage of folic acid preventable NTD cases1 as there are methodological problems in the studies indicating the association between the mutation and NTD. As the studies implicating 1 4 and refuting3 5 677→CT as a risk factor for NTD used almost identical methods, it is unlikely that the different results in different populations were due to methodological issues. We suggest that the different results reflect the real genetic variation between the populations.

    The results of this study indicate that 677→CT mutation is not responsible for NTD in Turkish patients. Further investigation is needed to elucidate the role of other mutations in either MTHFR or other folate related enzyme genes, which might be responsible for NTD.


    This study is supported by The Scientific and Technical Research Council of Turkey with a grant encoded “SBAG-1693”.


    Table 1

    Genotype and allele frequencies of MTHFR 677C→T in Turkish subjects

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