The prevalence of homozygous MTHFR polymorphism(s) in a Turkish university hospital population that necessitated MTHFR polymorphism investigation
More details
Hide details
Hacettepe University Faculty of Medicine, Department of Pediatrics, Ankara, Turkey
Hacettepe University Faculty of Medicine, Department of Obstetrics and Gynecology, Ankara, Turkey
Hacettepe University Faculty of Medicine, Department of Genetics, Ankara, Turkey
Hacettepe University Faculty of Medicine, Department of Biostatistics, Hacettepe University Medical School, Ankara, Turkey
Online publish date: 2018-04-15
Publish date: 2018-04-15
Electron J Gen Med 2018;15(4):em57
Methylenetetrahydrofolate reductase (MTHFR) polymorphisms may cause various medical disorders through different mechanisms. We aimed to determine the allelic frequency and the prevalence of homozygous MTHFR polymorphisms in a tertiary university hospital population that necessitated MTHFR polymorphism investigation owing to various reasons.

Our study consisted of 10449 patients who necessitated MTHFR polymorphism investigation owing to various reasons (coronary artery diseases, thrombotic events, epilepsy, migraine, repeated miscarriages, various obstetric complications) during 2008-2017.

The allelic frequency of MTHFR 677 and MTHFR 1298 mutations were 0.296 and 0.283 respectively. The prevalence of homozygous MTHFR C677T and MTHFR A1298C polymorphisms were 10.2 % and 11.1 %, respectively.

MTHFR polymorphisms are more frequent than was expected and one should be cautious when drawing disorder specific conclusions.

1. Harpel PC, Zhang X, Borth W. Homocysteine and hemostasis: pathogenetic mechanisms predisposing to thrombosis. The Journal of nutrition. 1996;126(4S):1285S. https://doi.org/10.1093/jn/126... PMid:8642472.
2. van Beynum IM, Kapusta L, den Heijer M, Vermeulen SH, Kouwenberg M, Daniëls O, et al. Maternal MTHFR 677C> T is a risk factor for congenital heart defects: effect modification by periconceptional folate supplementation. European heart journal. 2006;27(8):981-7. https://doi.org/10.1093/eurhea... PMid:16524890.
3. Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study. The American journal of medicine. 2004;117(1):26-31. https://doi.org/10.1016/j.amjm... PMid:15210385.
4. Caccamo D, Condello S, Gorgone G, Crisafulli G, Belcastro V, Gennaro S, et al. Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and risk of hyperhomocysteinemia. Neuromolecular medicine. 2004;6(2-3):117-26. https://doi.org/10.1385/NMM:6:....
5. Pan X, Wang P, Yin X, Liu X, Li D, Li X, et al. Association between maternal MTHFR polymorphisms and nonsyndromic cleft lip with or without cleft palate in offspring, a meta-analysis based on 15 case-control studies. International journal of fertility & sterility. 2015;8(4):463. https://doi.org/10.22074/ijfs.... PMid:25780529 PMCid:PMC4355933.
6. Dean J, Robertson Z, Reid V, Wang Q, Hailey H, Moore S, et al. A high frequency of the MTHFR 677C> T polymorphism in Scottish women with epilepsy: possible role in pathogenesis. Seizure. 2008;17(3):269-75. https://doi.org/10.1016/j.seiz... PMid:17904392.
7. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta‐analysis of published epidemiological studies. Journal of Thrombosis and Haemostasis. 2005;3(2):292-9. https://doi.org/10.1111/j.1538... PMid:15670035.
8. Hoffer LJ. Homocysteine remethylation and trans-sulfuration. Metabolism. 2004;53(11):1480-3. https://doi.org/10.1016/j.meta... PMid:15536605.
9. Stover PJ. One-carbon metabolism–genome interactions in folate-associated pathologies. The Journal of nutrition. 2009;139(12):2402-5. https://doi.org/10.3945/jn.109... PMid:19812215 PMCid:PMC2777484.
10. Turgal M, Yazicioglu A, Ozyuncu O, Beksac M. Impaired DNA methylation leading to heterotrisomy. Journal of Obstetrics and Gynaecology. 2013;33(8):904. https://doi.org/10.3109/014436... PMid:24219741.
11. Castro R, Rivera I, Ravasco P, Camilo M, Jakobs C, Blom H, et al. 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C→ T and 1298A→ C mutations are associated with DNA hypomethylation. Journal of medical genetics. 2004;41(6):454-8. https://doi.org/10.1136/jmg.20... PMid:15173232 PMCid:PMC1735802.
12. Şahin TG, Şahin N, Besler T, Beksaç S. Methionine Restricted Diet; Clinical Application. Gynecology Obstetrics & Reproductive Medicine. 2012;18(1):54-61.
13. Solanky N, Jimenez AR, D'Souza S, Sibley C, Glazier J. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta. 2010;31(2):134-43. https://doi.org/10.1016/j.plac... PMid:20036773.
14. Kosar A, Kasapoglu B, Kalyoncu S, Turan H, Balcik OS, Gümüs EI. Treatment of adverse perinatal outcome in inherited thrombophilias: a clinical study. Blood Coagulation & Fibrinolysis. 2011;22(1):14-8. https://doi.org/10.1097/MBC.0b... PMid:21042205.
15. Lykke J, Bare L, Olsen J, Lagier R, Arellano A, Tong C, et al. Thrombophilias and adverse pregnancy outcomes: results from the Danish National Birth Cohort. Journal of Thrombosis and Haemostasis. 2012;10(7):1320-5. https://doi.org/10.1111/j.1538... PMid:22578003.
16. McEwen BJ. Methylenetetrahydrofolate Reductase (MTHFR): mythology or polymorphism (ology)? Advances in Integrative Medicine. 2016;3(3):79-81. https://doi.org/10.1016/j.aime....
17. Perez ABA, D'Almeida V, Vergani N, de Oliveira AC, de Lima FT, Brunoni D. Methylenetetrahydrofolate reductase (MTHFR): incidence of mutations C677T and A1298C in Brazilian population and its correlation with plasma homocysteine levels in spina bifida. American Journal of Medical Genetics Part A. 2003;119(1):20-5. https://doi.org/10.1002/ajmg.a... PMid:12707953.
18. Sazci A, Ergul E, Kaya G, Kara I. Genotype and allele frequencies of the polymorphic methylenetetrahydrofolate reductase gene in Turkey. Cell biochemistry and function. 2005;23(1):51-4. https://doi.org/10.1002/cbf.11... PMid:15386535.
19. Ozarda Y, Sucu DK, Hizli B, Aslan D. Rate of T alleles and TT genotype at MTHFR 677C‐> T locus or C alleles and CC genotype at MTHFR 1298A‐> C locus among healthy subjects in Turkey: impact on homocysteine and folic acid status and reference intervals. Cell biochemistry and function. 2009;27(8):568-77. https://doi.org/10.1002/cbf.16... PMid:19764044.
20. Uçar F, Sönmez M, Ovalı E, Özmenoǧlu M, Kartı SS, Yılmaz M, et al. MTHFR C677T polymorphism and its relation to ischemic stroke in the Black Sea Turkish population. American journal of hematology. 2004;76(1):40-3. https://doi.org/10.1002/ajh.20... PMid:15114595.
21. Izmirli M, Inandiklioglu N, Abat D, Alptekin D, Demirhan O, Tansug Z, et al. MTHFR gene polymorphisms in bladder cancer in the Turkish population. Asian Pac J Cancer Prev. 2011;12(7):1833-5. PMid:22126575.
22. Çetintaş VB, Gündüz C. Association between polymorphism of MTHFR c. 677C> T and risk of cardiovascular disease in Turkish population: a meta-analysis for 2.780 cases and 3.022 controls. Molecular biology reports. 2014;41(1):397-409. https://doi.org/10.1007/s11033... PMid:24264431.
23. Caner M, Bircan R, Sevinç D, Benli F, Güney AI, Kurtoglu N. MTHFR, prothrombin and Factor V gene variants in Turkish patients with coronary artery stenosis. Genetics and Molecular Biology. 2008;31(4):836-8. https://doi.org/10.1590/S1415-....
24. Yasa MH, Bolaman Z, Yukselen V, Kadikoylu G, Karaoglul A, Batun S. Factor V Leiden G1691A, prothrombin G20210A, and MTHFR C677T mutations in Turkish inflammatory bowel disease patients. Hepato-gastroenterology. 2006;54(77):1438-42. PMID:17708272.
25. Sener EF, Oztop DB, Ozkul Y. MTHFR gene C677T polymorphism in autism spectrum disorders. Genetics research international. 2014;2014. http://dx.doi.org/10.1155/2014....
26. Deligezer U, Akisik EE, Dalay N. Homozygosity at the C677T of the MTHFR gene is associated with increased breast cancer risk in the Turkish population. in vivo. 2005;19(5):889-93.
27. Djordjevic V, Rakicevic L, Mikovic D, Kovac M, Miljic P, Radojkovic D, et al. Prevalence of factor V leiden, factor V cambridge, factor II G20210A and methylenetetrahydrofolate reductase C677T mutations in healthy and thrombophilic Serbian populations. Acta haematologica. 2004;112(4):227-9. https://doi.org/10.1159/000081... PMid:15564739.
28. Angelopoulou K, Nicolaides A, Constantinou Deltas C. Prevalence of genetic mutations that predispose to thrombophilia in a Greek Cypriot population. Clin Appl Thromb Hemost. 2000;6(2):104-7. https://doi.org/10.1177/107602... PMid:10775032.
29. Sazci A, Ergul E, Kaya G, Kara I. Genotype and allele frequencies of the polymorphic methylenetetrahydrofolate reductase gene in Turkey. Cell Biochem Funct. 2005;23(1):51-4. https://doi.org/10.1002/cbf.11... PMid:15386535.
30. Mao R, Fan Y, Chen F, Sun D, Bai J, Fu S. Methylenetetrahydrofolate reductase gene polymorphisms in 13 Chinese ethnic populations. Cell Biochem Funct. 2008;26(3):352-8. https://doi.org/10.1002/cbf.14... PMid:18098118.
31. Almawi WY, Finan RR, Tamim H, Daccache JL, Irani-Hakime N. Differences in the frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene among the Lebanese population. Am J Hematol. 2004;76(1):85-7. https://doi.org/10.1002/ajh.20... PMid:15114606.
32. Ekim M, Ekim H, Yilmaz YK. The prevalence of Factor V Leiden, prothrombin G20210A, MTHFR C677T and MTHFR A1298C mutations in healthy Turkish population. Hippokratia. 2015;19(4):309-13. PMid:27688694 PMCid:PMC5033140.