Polymorphism of folate-related genes and congenital heart diseases
Author Affiliations1Novosibirsk State Medical University of Minzdrav of Russia 630091, Novosibirsk, Krasny av., 52
2Institute of Circulation Pathology, of Minzdrav of Russia 630055, Novosibirsk, Rechkunovskaya str., 15
3Novosibirsk State Medical University, 630091, Novosibirsk, Krasny av., 52
4Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
5Institute of Cytology and Genetics of SB RAS, 630090, Novosibirsk, Prospekt Akademik Lavrentyev, 10; Institute of Internal and Preventive Medicine of SB RAMS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Abstract
Aim: To study the associations between polymorphism of folate metabolism genes with congenital heart diseases (CHD), paraclinical and clinical features. Methods: Children with congenital heart disease received surgical treatment at the clinic (225 boys and 225 girls). The 156 residents of Novosibirsk population sample aged 25-34 years were examined as a control to determine the population genotype frequencies of polymorphisms of MTHFR (C677T), MTRR (A66G), RFC1 (A80G), MTR (A2756G). Results: The differences in genotypes frequencies of SNPs of MTHFR, MTRR and RFC1 genes between patients with CHD and control have not been found. Statistically significant differences (p = 0.04) between compared groups were observed for А2756G polymorphism of MTR gene. The homozygous 677TT of the MTHFR gene were more frequent in patients with Fallo`s tetrad and other combined heart defects in both sexes. Boys with MTHFR 677CC genotype had lower frequency of conductivity abnormalities before operation then patients with two other genotypes (OR 0.37; 95 % CI 0.16-0.86; р = 0.009). It was also noted that patients with MTHFR 677TT genotype had higher frequency of AV blockade or atrial fibrillation after surgery (p = 0.01).
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References1. Viner A.S., Zhechev D.A., Kechin A.A. et al. Metabolism of folates and congenital malformations of development // Mat' i ditya v Kuzbasse. 2011. (2). 3-10. (in Russian)
2. Zhuchenko L.A. Primary population prevention of folate-dependent congenital malformations: abstract of thesis…doctor of medical sciences. Moscow, 2009. (in Russian)
3. Podzolkov V.P., Shvedunova V.N. Congenital heart diseases // Russkiy meditsinskiy zhurnal. 2001. 9. (10). 430-433. (in Russian)
4. Smith C., Klko S., Cantor C. Pulsed-field gel electrophoresis and the technology of large DNA molecules //Genome analysis. Ed. K. Davies, transl. from Eng. Moscow: Mir, 1990. 58-94. (in Russian)
5. Czeizel A.E. Primary prevention of neural-tube defects and some other major congenital abnormalities: recommendations for the appropriate use of folic acid during pregnancy // Paediatr. Drugs. 2000. 2. (6). 437-49.
6. Frosst P., Blom H.J., Milos R. et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase //Nature Genet. 1995. 10. 111-113.
7. Leclerc D., Rozen R. Molecular genetics of MTHFR: polymorphisms are not all benign // Med. Sci. 2007. 23. (3). 297-302.
8. MONICA Monograph and Multimedia Sourcebook. World,s largest study of heart disease, stroke, risk factors, and population trends 1979-2002. Edited by Hugh Tunstall-Pedoe (with 64 other contributors for the WHO MONICA Project) //WHO. Geneva. 2003. 237.
9. Nie Y., Gu H., Gong J. et al. Methylenetetrahydrofolate reductase C677T polymorphism and congenital heart disease: a meta-analysis // Clin. Chem. Lab. Med. 2011. 49. (12). 2101-2108.
10. Relton C.L., Wilding C.S., Pearce M.S. et al. Gene-gene interaction in folate-related genes and risk of neural tube defects in a UK population // J. Med. Genet. 2004. 41. (4). 256-260.
11. Shaw G.M., Zhu H., Lammer E.J. et al. Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial and conotruncal heart defects // Am. J. Epidemiol. 2003. 15. 158. (8). 747-752.
12. Strain J.J., Dowey L., Ward M. et al. B-vitamins, homocysteine metabolism and CVD // Proc. Nutr. Soc. 2004. 63. (4). 597-603.
13. Van Beynum I.M., den Heijer M., Blom H.J., Kapusta L. The MTHFR 677C->T polymorphism and the risk of congenital heart defects: a literature review and meta-analysis // QJM. 2007. 100. (12). 743-53.
14. Yin M., Dong L., Zheng J. et al. Meta analysis of the association between MTHFR C677T polymorphism and the risk of congenital heart defects // Ann. Hum. Genet. 2012. 76. (1). 9-16.
About Authors (Correspondence):
Maximov V.N. - doctor of medical sciences, head of the laboratory for molecular genetic studies of therapeutic diseases, e-mail: medik11@mail.ru
Polyakova I.V. - anaesthesiologist-resuscitation specialist, e-mail: liska-pol@mail.ru
Maximova J.V. - doctor of medical sciences, professor, head of the department of medical genetics and biology, e-mail: 164706@mail.ru
Koval O.N. - junior researcher of the laboratory for molecular genetic studies of therapeutic diseases, e-mail: oxen-ok@mail.ru
Voevoda M.I. - doctor of medical sciences, professor, corresponding member of RAMS, director, e-mail: mvoevoda@ya.ru
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