BibTex RIS Kaynak Göster

Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene

Yıl 2012, Cilt: 3 Sayı: 4, 472 - 476, 01.12.2012
https://doi.org/10.5799/ahinjs.01.2012.04.0205

Öz

Objectives: Relationship between several diseases and the mutations on the gene that is encoding MTHFR enzyme has been investigated. Studies are focused on the best known mutations; MTHFR C677T and A1298C. This study is planned for determining the frequency of C677T and A1298C polymorphism of MTHFR gene for individuals who have this kind of polymorphisms. Materials and methods: 164 individuals who were determined MTHFR polymorphism in Ankara Numune Education and Research Hospital Biochemistry Laboratory were included in the study. 44 of them were men and 120 of them were women. The mean of age of the patients were 48,4±16,8 year (18-76). MTHFR polymorphism was assayed by ROCHE Light Cycler 1.5 Real Time PCR. Results: In 109 of 164 patients (66.5%) MTHFR C677T polymorphisms were determined. While 89 of these patients (54.3%) were heterozygote, 20 of them were (12.2%) homozygote mutant type. In 95 patients (57.9%) A1298C mutation was determined, 76 (46.3%) were heterozygote and 19 of them (11.6%) had homozygote mutant genotype. Patients number with both mutations together was 40 (24.4%). In the study group, no difference was found in frequency of MTHFR C677T and MTHFR A1298C polymorphisms (p>0.05). Conclusions: In our study, it is seen that in individuals determined polymorphism, even MTHFR A1298C polymorphism can be found as frequent as C677T polymorphism.

Kaynakça

  • Homberger G, Linnebank M, Winter C. Genomic struc- ture and transcript variants of the human methylene- tetrahydrofolate reductase gene. Eur J Hum Genet 2000;(8): 725-9.
  • Fodinger M, Horl WH, Sunder-Plassman G. Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol 2000;13(1):20-33.
  • Goyette P, Rozen R. The thermolabile variant 677CT can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofo- late reductase. Hum Mutat 2000;16(1):132-8.
  • Sibani S, Christensen B, O’ferrall E, et al. Character- ization of six novel mutations in the methylenetetra- hydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat 2000;27(15): 280-7.
  • Rozen R. Methylenetetrahydrofolate reductase in vas- cular dısease, neural tube defects and colon cancer. IV.Reunion, Metiyonin metabolism, molecular mech- anisms and clinical implications.1998; Index no 6, March 1-5, University of Nevarra and Granada, Spain.
  • Bagley PJ, Jacob S. A common mutation in the methy- lenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Med Sci 1998;24(95):13217-20.
  • Peng F, Labelle LA, Rainey B, et al. Single nucleotide polymorpisms ın the methylenetetrahydrofolate re- ductase gene are common in US Caucasian and His- panic American populations. Int J Mol Med 2001;8(5): 509-11.
  • Rady PL, Tyring SK, Hundnall SD, et al. Methylenetet- rahydrofolate reductase (MTHFR): The incidence of mutations C677T and A1298C in the Ashkenazi Jew- ish population. Am J Med Genet 1999; 86(2):380-8
  • Tonetti C, Burtscher A, Bories D, et al. Methylenetet- rahydrofolate reductase deficiency in four siblings: A clinical, biochemical, and molecular study of the fam- ily. Am J Med Genet 2000; 91(3):363-7.
  • Goyette P, Pai A, Milos R, et al. Gene structure of human mouse methylenetetrahydrofolate reductase (MTHFR). Mammalian Genome 1998;9(5):652-6.
  • Schneider JA, Rees DC, Liu YT, et al. Worldwide distributionof a common methylenetetrahydrofolate eductase mutation. Am J Hum Genet 1998;(62):1258- 1260.
  • Sell SM, Lugemwa PR. Development of a higly ac- curate, rapid PCR-RFLP genotyping assay for the methylenetetrahydrofolate reductase gene. Genet Test 1999;21(3):287-9.
  • Demuth K, Moatti N, Hanon O, et al . Opposite effects of plasma homocysteine and the methylenetetrahy- drofolate reductase C677T mutation on carotid artery geometry in asymptomatic adults. Thromb Vasc Biol, 1998;12(18):1838-43.
  • Stern LL, Bagley PJ, Rosenberg IH, et al.Conversion of 5-formyltetrahydrofolic acid is unimpaired in folate- adequate persons homozygous for the C677T muta- tion in the methylenetetrahydrofolate reductase gene. J Nutr 2000;130(12): 2238-42.
  • Molloy AM, Daly S, Mills JL, et al. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associ- ated with low red-cell folates: Implications for folate intake recommendations. Lancet 1997;49(11):1591-3.
  • Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate re- ductase gene variants and congenital anomalies: Am J Epidemiol 2000;151(7):862-77.
  • Shpichinetsky V, Raz I, Friedlander Y, et al. The as- sociation between two common mutations C677T and A1298C in human methylenetetrahydrofolate reduc- tase gene and the risk for diabetic nephropathy in type II diabetic patients. J Nutr 2000;130(12):2493-7.
  • Langman LJ, Wong BYY, Boggis C, et al. The preva- lence and linkage disequilibrium of three methylene- tetrahydrofolate reductase (MTHFR) gene polymor- phisms varies in difrent ethnic groups presented at INABIS’98-5th Internet World Congress on Biomedi- cal Sciences at McMaster University, Canada, Dec 7-16th.
  • Kim Y. Methylenetetrahydrofolate reductase poly- morphisms, folate, and cancer risk: A paradigm of gene-nutrient interactions in carcinogenesis. Nutr Rev 2000;58(2):205-17.
  • Sazci A, Ergul E, Kaya G, Kara I. Genotype and allele frequencies of the polymorphic methylenetetrahydro- folate reductase gene in Turkey. Cell Biochem Funct 2005;23(1):51-4.
  • Frosst P, Blom HJ, Milos R, Goyette P, et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate re- ductase. Nat Genet 2011;10(1):111-3.
  • Sacchi E, Tagliabue L, Duca F, Mannucci PM. High frequency of the C677T mutation in the methylene- tetrahydrofolate reductase (MTHFR) gene in Northern Italy (letter). Thromb Haemost 1997;78(9):963-4.
  • Kluijtmans LA, Van Den Heuvel LP, Boers GH, et al. Molecular genetic analysis in mild hyperhomocyste- inemia: a common mutation in the methylenetetra- hydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996; 58(1):35-41.
  • Franco RF, Araujo AG, Guerrerio JF, Elion J, Zago MA. Analysis of the 677 C>T mutation of the methy- lenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost 1998; (79):119-21.
  • Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylene- tetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998;64(2):169-72.
  • Viel A, Dallagnese L, Simone F, et al. Loss of hetero- zygosity at the 5,10-methylenetetrahydrofolate reduc- tase locus in human ovarian carcinomas. Br J Cancer 1997;75(10):1105-10.
  • Koçak N, Özen F,Yıldırım EM, Özdemir Ö. Metilente- trahidrofolat Redüktaz (Mthfr) C677T ve A1298C Gen Polimorfizmleri. İnönü Üniversitesi Tıp Fakültesi Der- gisi 2009;16(3):157-61.
  • Ozarda Y,Sucu DK,Hizli B, Aslan D . Rate of T alleles and TT genotype at MTHFR 677C->T locus or C al- leles and CC genotype at MTHFR 1298A->C locus among healthy subjects in Turkey: impact on homo- cysteine and folic acid status and reference intervals. Cell Biochem Funct 2009;27(8):568-77.

Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene

Yıl 2012, Cilt: 3 Sayı: 4, 472 - 476, 01.12.2012
https://doi.org/10.5799/ahinjs.01.2012.04.0205

Öz

Amaç: MTHFR enzimi 5,10 metilentetrahidrofolatı 5 metiltetrahidrofolata katalize ederek, homosisteinden metionin remetilasyonu için gerekli olan aktif folat formunu oluşturur. Bu enzimi kodlayan gendeki mutasyonlar ile bir çok hastalık arasındaki ilişki araştırılmaktadır. Çalışmalar, en iyi bilinen MTHFR C677T ve A1298C polimorfizmleri üzerinde yoğunlaşmaktadır. Bu çalışma, MTHFR geninde C677T ve A1298C polimorfizm tespit edilen bireylerde bu polimorfizmlerin sıklığını saptamak amacıyla planlanmıştır. Gereç ve yöntem: Çalışmaya, Ankara Numune Eğitim ve Araştırma Hastanesi III Biyokimya Laboratuvarı\'nda C677T ve A1298C yönünden MTHFR polimorfizmi saptanan toplam 164 birey dahil edildi. Hastaların 44\'ü erkek, 120\'si kadındı. Tüm hastaların yaş ortalaması 48,4±16,8 yıl (yaş aralığı 18-76) idi. MTHFR polimorfizmi, ROCHE Light Cycler 1.5 Real Time PCR ile çalışıldı. Bulgular: Çalışmaya alınan 164 polimorfizmli bireyin 109\'unda (% 66,5) MTHFR C677T polimorfizmi saptandı. Bu bireylerin 89\'u (% 54,3) heterozigot iken 20\'si (%12,2) homozigot mutant tipti. Yine 95 (%57,9) bireyde A1298C polimorfizmi tespit edildi. Bunların 76\'sı (%46,3) heterozigot, 19\'u (% 11,6) homozigot mutant genotipe sahipti. Her iki polimorfizmin heterozigot birlikte bulunduğu hasta sayısı 40 (% 24,4) idi. Çalışma grubunda, MTHFR C677T ve MTHFR A1298C polimorfizm sıklıkları açısından fark tespit edilmedi (p>0,05). Sonuç: Çalışmamızda, polimorfizm tespit edilen bireylerde, MTHFR A1298C polimorfizminin de C677T kadar sık bulunabileceği görüldü.

Kaynakça

  • Homberger G, Linnebank M, Winter C. Genomic struc- ture and transcript variants of the human methylene- tetrahydrofolate reductase gene. Eur J Hum Genet 2000;(8): 725-9.
  • Fodinger M, Horl WH, Sunder-Plassman G. Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol 2000;13(1):20-33.
  • Goyette P, Rozen R. The thermolabile variant 677CT can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofo- late reductase. Hum Mutat 2000;16(1):132-8.
  • Sibani S, Christensen B, O’ferrall E, et al. Character- ization of six novel mutations in the methylenetetra- hydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat 2000;27(15): 280-7.
  • Rozen R. Methylenetetrahydrofolate reductase in vas- cular dısease, neural tube defects and colon cancer. IV.Reunion, Metiyonin metabolism, molecular mech- anisms and clinical implications.1998; Index no 6, March 1-5, University of Nevarra and Granada, Spain.
  • Bagley PJ, Jacob S. A common mutation in the methy- lenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Med Sci 1998;24(95):13217-20.
  • Peng F, Labelle LA, Rainey B, et al. Single nucleotide polymorpisms ın the methylenetetrahydrofolate re- ductase gene are common in US Caucasian and His- panic American populations. Int J Mol Med 2001;8(5): 509-11.
  • Rady PL, Tyring SK, Hundnall SD, et al. Methylenetet- rahydrofolate reductase (MTHFR): The incidence of mutations C677T and A1298C in the Ashkenazi Jew- ish population. Am J Med Genet 1999; 86(2):380-8
  • Tonetti C, Burtscher A, Bories D, et al. Methylenetet- rahydrofolate reductase deficiency in four siblings: A clinical, biochemical, and molecular study of the fam- ily. Am J Med Genet 2000; 91(3):363-7.
  • Goyette P, Pai A, Milos R, et al. Gene structure of human mouse methylenetetrahydrofolate reductase (MTHFR). Mammalian Genome 1998;9(5):652-6.
  • Schneider JA, Rees DC, Liu YT, et al. Worldwide distributionof a common methylenetetrahydrofolate eductase mutation. Am J Hum Genet 1998;(62):1258- 1260.
  • Sell SM, Lugemwa PR. Development of a higly ac- curate, rapid PCR-RFLP genotyping assay for the methylenetetrahydrofolate reductase gene. Genet Test 1999;21(3):287-9.
  • Demuth K, Moatti N, Hanon O, et al . Opposite effects of plasma homocysteine and the methylenetetrahy- drofolate reductase C677T mutation on carotid artery geometry in asymptomatic adults. Thromb Vasc Biol, 1998;12(18):1838-43.
  • Stern LL, Bagley PJ, Rosenberg IH, et al.Conversion of 5-formyltetrahydrofolic acid is unimpaired in folate- adequate persons homozygous for the C677T muta- tion in the methylenetetrahydrofolate reductase gene. J Nutr 2000;130(12): 2238-42.
  • Molloy AM, Daly S, Mills JL, et al. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associ- ated with low red-cell folates: Implications for folate intake recommendations. Lancet 1997;49(11):1591-3.
  • Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate re- ductase gene variants and congenital anomalies: Am J Epidemiol 2000;151(7):862-77.
  • Shpichinetsky V, Raz I, Friedlander Y, et al. The as- sociation between two common mutations C677T and A1298C in human methylenetetrahydrofolate reduc- tase gene and the risk for diabetic nephropathy in type II diabetic patients. J Nutr 2000;130(12):2493-7.
  • Langman LJ, Wong BYY, Boggis C, et al. The preva- lence and linkage disequilibrium of three methylene- tetrahydrofolate reductase (MTHFR) gene polymor- phisms varies in difrent ethnic groups presented at INABIS’98-5th Internet World Congress on Biomedi- cal Sciences at McMaster University, Canada, Dec 7-16th.
  • Kim Y. Methylenetetrahydrofolate reductase poly- morphisms, folate, and cancer risk: A paradigm of gene-nutrient interactions in carcinogenesis. Nutr Rev 2000;58(2):205-17.
  • Sazci A, Ergul E, Kaya G, Kara I. Genotype and allele frequencies of the polymorphic methylenetetrahydro- folate reductase gene in Turkey. Cell Biochem Funct 2005;23(1):51-4.
  • Frosst P, Blom HJ, Milos R, Goyette P, et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate re- ductase. Nat Genet 2011;10(1):111-3.
  • Sacchi E, Tagliabue L, Duca F, Mannucci PM. High frequency of the C677T mutation in the methylene- tetrahydrofolate reductase (MTHFR) gene in Northern Italy (letter). Thromb Haemost 1997;78(9):963-4.
  • Kluijtmans LA, Van Den Heuvel LP, Boers GH, et al. Molecular genetic analysis in mild hyperhomocyste- inemia: a common mutation in the methylenetetra- hydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996; 58(1):35-41.
  • Franco RF, Araujo AG, Guerrerio JF, Elion J, Zago MA. Analysis of the 677 C>T mutation of the methy- lenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost 1998; (79):119-21.
  • Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylene- tetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998;64(2):169-72.
  • Viel A, Dallagnese L, Simone F, et al. Loss of hetero- zygosity at the 5,10-methylenetetrahydrofolate reduc- tase locus in human ovarian carcinomas. Br J Cancer 1997;75(10):1105-10.
  • Koçak N, Özen F,Yıldırım EM, Özdemir Ö. Metilente- trahidrofolat Redüktaz (Mthfr) C677T ve A1298C Gen Polimorfizmleri. İnönü Üniversitesi Tıp Fakültesi Der- gisi 2009;16(3):157-61.
  • Ozarda Y,Sucu DK,Hizli B, Aslan D . Rate of T alleles and TT genotype at MTHFR 677C->T locus or C al- leles and CC genotype at MTHFR 1298A->C locus among healthy subjects in Turkey: impact on homo- cysteine and folic acid status and reference intervals. Cell Biochem Funct 2009;27(8):568-77.
Toplam 28 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Araştırma Yazısı
Yazarlar

Nihal Uğuz Bu kişi benim

Gönül Erden Bu kişi benim

Oya Güngör Bu kişi benim

Ceylan Bal Bu kişi benim

Metin Yıldırımkaya Bu kişi benim

Yayımlanma Tarihi 1 Aralık 2012
Yayımlandığı Sayı Yıl 2012 Cilt: 3 Sayı: 4

Kaynak Göster

APA Uğuz, N., Erden, G., Güngör, O., Bal, C., vd. (2012). Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene. Journal of Clinical and Experimental Investigations, 3(4), 472-476. https://doi.org/10.5799/ahinjs.01.2012.04.0205
AMA Uğuz N, Erden G, Güngör O, Bal C, Yıldırımkaya M. Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene. J Clin Exp Invest. Aralık 2012;3(4):472-476. doi:10.5799/ahinjs.01.2012.04.0205
Chicago Uğuz, Nihal, Gönül Erden, Oya Güngör, Ceylan Bal, ve Metin Yıldırımkaya. “Determination of the Frequency of MTHFR C677T and MTHFR A1298C Polymorphisms in Persons With Polymorphic MTHFR Gene”. Journal of Clinical and Experimental Investigations 3, sy. 4 (Aralık 2012): 472-76. https://doi.org/10.5799/ahinjs.01.2012.04.0205.
EndNote Uğuz N, Erden G, Güngör O, Bal C, Yıldırımkaya M (01 Aralık 2012) Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene. Journal of Clinical and Experimental Investigations 3 4 472–476.
IEEE N. Uğuz, G. Erden, O. Güngör, C. Bal, ve M. Yıldırımkaya, “Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene”, J Clin Exp Invest, c. 3, sy. 4, ss. 472–476, 2012, doi: 10.5799/ahinjs.01.2012.04.0205.
ISNAD Uğuz, Nihal vd. “Determination of the Frequency of MTHFR C677T and MTHFR A1298C Polymorphisms in Persons With Polymorphic MTHFR Gene”. Journal of Clinical and Experimental Investigations 3/4 (Aralık 2012), 472-476. https://doi.org/10.5799/ahinjs.01.2012.04.0205.
JAMA Uğuz N, Erden G, Güngör O, Bal C, Yıldırımkaya M. Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene. J Clin Exp Invest. 2012;3:472–476.
MLA Uğuz, Nihal vd. “Determination of the Frequency of MTHFR C677T and MTHFR A1298C Polymorphisms in Persons With Polymorphic MTHFR Gene”. Journal of Clinical and Experimental Investigations, c. 3, sy. 4, 2012, ss. 472-6, doi:10.5799/ahinjs.01.2012.04.0205.
Vancouver Uğuz N, Erden G, Güngör O, Bal C, Yıldırımkaya M. Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene. J Clin Exp Invest. 2012;3(4):472-6.