Orsolya Biró MSc, Farkas Cecilia MSc, Prof. Dr. János Rigó Jr.
First Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
Background: International recommendations emphasize the importance of adequate folic acid intake, however, the question of dietary supplements usually arise only at the beginning of pregnancy. Defective folate metabolism has been associated with fetal anomalies including congenital heart disease (CHD). In the first study, the frequency of MTHFR gene polymorphisms and folic acid intake were estimated in women of reproductive age. In the subsequent case-control study, we evaluated the MTHFR C677T/A1298C, MTR A2756G, and MTRR A66G polymorphisms as risk factors for CHD.
Methods: In the first study, genotypes were determined of 34 non-pregnant women by RT-PCR and allele frequencies were calculated. Folic acid intake and potential risks of interactions (e.g. hormonal contraceptives) were measured. In the second study, genotypes were assessed in maternal and fetal sample groups from 20 vs. 20, and 19 vs. 19 case-control pregnancies. Odds ratios were calculated for CHD in each case.
Results: 65% of non-pregnant women carried 2 mutant MTHFR alleles, resulting in reduced enzyme activity. The 677T allele frequency was 10% above the European average, and the folic acid intake was critically low. There was no significant difference in the frequencies of MTHFR polymorphisms in the maternal case-control group. Interestingly, bearing the MTRR 66G allele reduced the risk of CHD. In the prenatal case-control group, the MTHFR 1298C allele turned out as a possible risk factor and the MTRR 66G allele appeared as a protective factor.
Conclusion: Based on our study, the frequency of MTHFR mutations and associated environmental factors are considerable. The investigated gene polymorphisms carried different levels of risk in case of maternal or fetal involvement. We have not found significant associations between maternal MTHFR polymorphisms and CHD, possibly due to the protective effect of folic acid supplements. Prenatally, the MTHFR 1298C allele turned out as a possible risk factor for developing CHD.
Doctoral School: Clinical Medicine Doctoral School,
Program: Reproductive Medicine
Supervisor: János Rigó Jr.
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