Influence of folate cycle genes polymorphism on pregnancy complications in women of kazakh ethnic group
71 77
Keywords:
gene polymorphism, MTR, MTRR, MTHFR, pregnancy complicationsAbstract
The study was conducted to study the frequency distribution of alleles and genotypes of polymorphic variants of folate cycle genes methionine synthase (MTR) A2756G, rs1805087; methionine synthase reductase (MTRR) A66G, rs1801394; and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T, rs1801133in women of the Kazakh ethnic group with pregnancy complications. The research was conducted using the "case-control study". The test group was consisted by 121 pregnant women who had in anamnesis complications in the first two or more pregnancies, including miscarriages. The control group was consisted by 120 pregnant women who had two or more normal outcomes of the first two pregnancies without pregnancy complications in anamnesis. The material of the study was genomic DNA isolated from the venous blood of the examined women. The definition of genetic polymorphisms was carried out on the RealTime CFX96 amplifiers (BioRad, USA). Statistical analysis in the online-program SNPstats using the codominant, dominant, recessive, overdominant and log-additive inheritance models revealed no statistically significant differences in the frequencies of the observed polymorphisms in the women of the test and control groups. The obtained results of the studies indicate supplementing information on the prevalence of the polymorphic alleles of the folate cycle genes MTR, MTRR, MTHFR among women of the Kazakh ethnic group. However, further molecular epidemiological studies are needed to unambiguously interpret the contribution of environmental and genetic factors to the course of pregnancy.
References
1. Ford, H. B., Schust, D. J. Recurrent pregnancy loss: etiology, diagnosis, and therapy // Rev. Obstet Gynecol. – 2009. – № 2. – P. 76 – 83.
2. Tamura T., Picciano M.F. Folate and human reproduction // Am. J Clin. Nutr. – 2006. – Vol. 83. – P. 993–1016.
3. Molloy A.M. Folate and homocysteine interrelationships including genetics of the relevant enzymes// Curr. Opin. Lipidol. – 2004. – Vol. 15. – № 1. – P. 49–57.
4. Molloy A.M. Genetic aspects of folate metabolism // Subcell Biochem.– 2012. – Vol. 56. – № 105. – P. 30.
5. Barbosa, P. R., Stabler, S. P., Machado, A. L. et al. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphismsas determinats for elevated total homocysteine concentrations in pregnant women // Eur. J. Clin. Nutr. – 2008. – Vol. 62. – № 8. – Р. 1010–1121.
6. Forges T., Monnier–Barbarino P., Alberto J. M. et al. Impact of folate and homocysteine metabolism on human reproductive health // Hum. Reprod. – 2007. – Vol. 13. – № 3. – P. 225–238.
7. Rosenblatt D. S. Folate and homocysteine metabolism and gene polymorphisms in the etiology of Down syn-drome. Am. J. Clin. Nutrition. – 1999. – Vol. 70. – № 4. – P. 429–430.
8. Binia A., Contreras A., Canizales–Quinteros S. et al. Geographical and ethnic distribution of single nucleotide polymorphisms within genes of the folate/homocysteine pathway metabolism // Genes Nutr. – 2014. – Vol. 9. – № 5. – P. 421.
9. Рапильбекова Г. К., Мамедалиева Н.М. Роль тромбофилии в генезе синдрома потери плода у женщин казахской популяции // Журнал акушерства и женских болезней. – 2006. – № 3. – С. 31–34.
10. Slager S.L., Schaid D.J. Evaluation of candidate genes in case–control studies: a statistical method to account for related subjects // Am. J. Hum. Genet. – 2001. – Vol. 68. – P 1457–1462.
11. Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies // Bi-oinformatics – 2006. – Vol. 22. – № 15. – P. 1928–1929.
12. Kim J.H., et al. Association of methionine synthase and thymidylate synthase genetic polymorphisms with idi-opathic recurrent pregnancy loss // Fertil. Steril. – 2013. – P. 1674–1680.
13. Guo Q.N., et al. Association of methionine synthase reductase gene polymorphism with unexplained recurrent spontaneous abortion // Zhonghua Fu Chan Ke Za Zhi. – 2012. – № 10. – Р. 742–746.
14. Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences // Am J Pharmacogenomics. – 2001. – Vol 1. – №3. – P. 189–201.
15. Bae, J., Shin, S.J., Cha, S.H. et al. Prevalent genotypes ofmethylenetetrahydrofolatereductase (MTHFR C677T and A1298C) inspontaneously aborted embryos // Fertility and Sterility. – 2007. – Vol. 87. – № 2. – P. 351–355.
16. Engel, S.M., Olshan, A.F., Siega–RIZ, et al. Polymorphisms in folate metabolizing genes and risk for sponta-neous preterm and small–forgestationalage birth // Am. J. Obstet. Gynecol. – 2001. – Vol. 95. – P. 1231–1251.
17. Holmes, Z. R., Regan L., Chilcott, I., Cohen, H. The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss // Br. J. Haematol. – 1999. – Vol. 105. – P. 98–101.
18. Wu, X., Zhao, L., Zhu, H. et al. Association between the MTHFR C677 Tpolymorphism and recurrent preg-nancy loss: a meta–analysis // Genet Test Mol. Biomarkers. – 2012. – Vol. 16. – № 7. – Р. 806–811.
19. Botto L., Yang Q. 5,10–Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a huge review // Am J Epidemiol. – 2000. – Vol. 151. – № 9. – Р. 862–877.
20. Fodinger M., Horl W., Sunder–Plassmann G. Molecular biology of 5,10–methylenetetrahydrofolate reductase // J. Nephrol. – 1999. – № 13. – Р. 1–17.
21. Wilcken B., Bamforth F., Li Z. et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methyl-enetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide // J. Med. Genet. – 2003. – Vol. 40. – P. 619–625.
References
1. Ford HB, Schust DJ (2009) Recurrent pregnancy loss: etiology, diagnosis, and therapy, Rev. Obstet Gynecol, No 2, pp. 76–83.
2. Tamura T, Picciano MF (2006) Folate and human reproduction, Am. J Clin. Nutr, Vol. 83, pp. 993–1016.
3. Molloy AM (2004) Folate and homocysteine interrelationships including genetics of the relevant enzymes, Curr. Opin. Lipidol, Vol. 15, No 1, pp 49–57.
4. Molloy AM (2012) Genetic aspects of folate metabolism, Subcell Biochem, Vol. 56, No 105, pp 30.
5. Barbosa PR, Stabler SP, Machado AL. et al (2008) Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphismsas determinats for elevated total homocysteine concentrations in pregnant women, Eur. J. Clin. Nutr, Vol. 62, No 8, pp. 1010–1121.
6. Forges T, Monnier–Barbarino PP, Alberto JM. et al (2008) Impact of folate and homocysteine metabolism on human repproductive health, Hum. Repprod, Vol. 13, No 3, рр. 225–238.
7. Rosenblatt DS (1999) Folate and homocysteine metabolism and gene ppolymorpphisms in the etiology of Down syndrome, Am. J. Clin. Nutrition, Vol. 70, No 4, рр. 429–430.
8. Binia A, Contreras A, Canizales–Quinteros S. et al (2014) Geograpphical and ethnic distribution of single nu-cleotide ppolymorphisms within genes of the folate/homocysteine pathway metabolism, Genes Nutr, Vol.9, No 5, рр. 421.
9. Rappilbekоva GK, Mamedalieva NM (2006) The rоle оf thrоmbоpphilia in the genesis оf fetal lоss syndrоme in wоmen оf the Kazakh ppоppulatiоn, Jоurnal оf Оbstetrics and Wоmen's Diseases, Nо. 3, pp. 31-34.
10. Slager SL, Schaid DJ (2001) Evaluation of candidate genes in case–control studies: a statistical method to ac-count for related subjects, Am. J. Hum. Genet, Vol. 68, рр. 1457–1462.
11. Solé X, Guinó E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies, Bioinformatics, Vol. 22, No 15, рр. 1928–1929.
12. Kim JH, et al (20130 Association of methionine synthase and thymidylate synthase genetic ppolymorpphisms with idiopathic recurrent pregnancy loss, Fertil. Steril, рр. 1674–1680.
13. Guo QN, et al (2012) Association of methionine synthase reductase gene polymorphism with unexplained re-current spontaneous abortion, Zhonghua Fu Chan Ke Za Zhi, No 10, рр. 742–746.
14. Schwahn B, Rozen R (2001) Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical conse-quences // Am J Pharmacogenomics. – 2001. – Vol 1. – No3. – PP. 189–201.
15. Bae J, Shin SJ, Cha SH. et al (2007) Prevalent genotypes of methylenetetrahydrofolatereductase (MTHFR C677T and A1298C) inspontaneously aborted embryos, Fertility and Sterility, Vol. 87, No 2, рр. 351–355.
16. Engel SM, Olshan AF et al (2001) Polymorphisms in folate metabolizing genes and risk for spontaneous pre-term and small–for gestational age birth, Am. J. Obstet. Gynecol, Vol. 95, рр. 1231–1251.
17. Holmes ZR, Regan L, Chilcott I, Cohen H (1999) The C677T MTHFR gene mutation is not ppredictive of risk for recurrent fetal loss, Br. J. Haematol, Vol. 105, рр. 98–101.
18. Wu X, Zhao L, Zhu H et al (2012) Association between the MTHFR C677 Tppolymorpphism and recurrent ppregnancy loss: a meta–analysis, Genet Test Mol. Biomarkers, Vol. 16, No 7, рр. 806–811.
19. Botto L, Yang Q (2000) 5,10–Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a huge review, Am J Eppidemiol, Vol. 151, No 9, рр. 862–877.
20. Fodinger M, Horl W, Sunder–Plassmann G (1999) Molecular biology of 5,10–methylenetetrahydrofolate re-ductase, J. Nepphrol, No 13, рр. 1–17.
21. Wilcken B, Bamforth F, Li Z et al (2003) Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide, J. Med. Genet, Vol. 40, рр. 619–625.
2. Tamura T., Picciano M.F. Folate and human reproduction // Am. J Clin. Nutr. – 2006. – Vol. 83. – P. 993–1016.
3. Molloy A.M. Folate and homocysteine interrelationships including genetics of the relevant enzymes// Curr. Opin. Lipidol. – 2004. – Vol. 15. – № 1. – P. 49–57.
4. Molloy A.M. Genetic aspects of folate metabolism // Subcell Biochem.– 2012. – Vol. 56. – № 105. – P. 30.
5. Barbosa, P. R., Stabler, S. P., Machado, A. L. et al. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphismsas determinats for elevated total homocysteine concentrations in pregnant women // Eur. J. Clin. Nutr. – 2008. – Vol. 62. – № 8. – Р. 1010–1121.
6. Forges T., Monnier–Barbarino P., Alberto J. M. et al. Impact of folate and homocysteine metabolism on human reproductive health // Hum. Reprod. – 2007. – Vol. 13. – № 3. – P. 225–238.
7. Rosenblatt D. S. Folate and homocysteine metabolism and gene polymorphisms in the etiology of Down syn-drome. Am. J. Clin. Nutrition. – 1999. – Vol. 70. – № 4. – P. 429–430.
8. Binia A., Contreras A., Canizales–Quinteros S. et al. Geographical and ethnic distribution of single nucleotide polymorphisms within genes of the folate/homocysteine pathway metabolism // Genes Nutr. – 2014. – Vol. 9. – № 5. – P. 421.
9. Рапильбекова Г. К., Мамедалиева Н.М. Роль тромбофилии в генезе синдрома потери плода у женщин казахской популяции // Журнал акушерства и женских болезней. – 2006. – № 3. – С. 31–34.
10. Slager S.L., Schaid D.J. Evaluation of candidate genes in case–control studies: a statistical method to account for related subjects // Am. J. Hum. Genet. – 2001. – Vol. 68. – P 1457–1462.
11. Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies // Bi-oinformatics – 2006. – Vol. 22. – № 15. – P. 1928–1929.
12. Kim J.H., et al. Association of methionine synthase and thymidylate synthase genetic polymorphisms with idi-opathic recurrent pregnancy loss // Fertil. Steril. – 2013. – P. 1674–1680.
13. Guo Q.N., et al. Association of methionine synthase reductase gene polymorphism with unexplained recurrent spontaneous abortion // Zhonghua Fu Chan Ke Za Zhi. – 2012. – № 10. – Р. 742–746.
14. Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences // Am J Pharmacogenomics. – 2001. – Vol 1. – №3. – P. 189–201.
15. Bae, J., Shin, S.J., Cha, S.H. et al. Prevalent genotypes ofmethylenetetrahydrofolatereductase (MTHFR C677T and A1298C) inspontaneously aborted embryos // Fertility and Sterility. – 2007. – Vol. 87. – № 2. – P. 351–355.
16. Engel, S.M., Olshan, A.F., Siega–RIZ, et al. Polymorphisms in folate metabolizing genes and risk for sponta-neous preterm and small–forgestationalage birth // Am. J. Obstet. Gynecol. – 2001. – Vol. 95. – P. 1231–1251.
17. Holmes, Z. R., Regan L., Chilcott, I., Cohen, H. The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss // Br. J. Haematol. – 1999. – Vol. 105. – P. 98–101.
18. Wu, X., Zhao, L., Zhu, H. et al. Association between the MTHFR C677 Tpolymorphism and recurrent preg-nancy loss: a meta–analysis // Genet Test Mol. Biomarkers. – 2012. – Vol. 16. – № 7. – Р. 806–811.
19. Botto L., Yang Q. 5,10–Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a huge review // Am J Epidemiol. – 2000. – Vol. 151. – № 9. – Р. 862–877.
20. Fodinger M., Horl W., Sunder–Plassmann G. Molecular biology of 5,10–methylenetetrahydrofolate reductase // J. Nephrol. – 1999. – № 13. – Р. 1–17.
21. Wilcken B., Bamforth F., Li Z. et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methyl-enetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide // J. Med. Genet. – 2003. – Vol. 40. – P. 619–625.
References
1. Ford HB, Schust DJ (2009) Recurrent pregnancy loss: etiology, diagnosis, and therapy, Rev. Obstet Gynecol, No 2, pp. 76–83.
2. Tamura T, Picciano MF (2006) Folate and human reproduction, Am. J Clin. Nutr, Vol. 83, pp. 993–1016.
3. Molloy AM (2004) Folate and homocysteine interrelationships including genetics of the relevant enzymes, Curr. Opin. Lipidol, Vol. 15, No 1, pp 49–57.
4. Molloy AM (2012) Genetic aspects of folate metabolism, Subcell Biochem, Vol. 56, No 105, pp 30.
5. Barbosa PR, Stabler SP, Machado AL. et al (2008) Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphismsas determinats for elevated total homocysteine concentrations in pregnant women, Eur. J. Clin. Nutr, Vol. 62, No 8, pp. 1010–1121.
6. Forges T, Monnier–Barbarino PP, Alberto JM. et al (2008) Impact of folate and homocysteine metabolism on human repproductive health, Hum. Repprod, Vol. 13, No 3, рр. 225–238.
7. Rosenblatt DS (1999) Folate and homocysteine metabolism and gene ppolymorpphisms in the etiology of Down syndrome, Am. J. Clin. Nutrition, Vol. 70, No 4, рр. 429–430.
8. Binia A, Contreras A, Canizales–Quinteros S. et al (2014) Geograpphical and ethnic distribution of single nu-cleotide ppolymorphisms within genes of the folate/homocysteine pathway metabolism, Genes Nutr, Vol.9, No 5, рр. 421.
9. Rappilbekоva GK, Mamedalieva NM (2006) The rоle оf thrоmbоpphilia in the genesis оf fetal lоss syndrоme in wоmen оf the Kazakh ppоppulatiоn, Jоurnal оf Оbstetrics and Wоmen's Diseases, Nо. 3, pp. 31-34.
10. Slager SL, Schaid DJ (2001) Evaluation of candidate genes in case–control studies: a statistical method to ac-count for related subjects, Am. J. Hum. Genet, Vol. 68, рр. 1457–1462.
11. Solé X, Guinó E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies, Bioinformatics, Vol. 22, No 15, рр. 1928–1929.
12. Kim JH, et al (20130 Association of methionine synthase and thymidylate synthase genetic ppolymorpphisms with idiopathic recurrent pregnancy loss, Fertil. Steril, рр. 1674–1680.
13. Guo QN, et al (2012) Association of methionine synthase reductase gene polymorphism with unexplained re-current spontaneous abortion, Zhonghua Fu Chan Ke Za Zhi, No 10, рр. 742–746.
14. Schwahn B, Rozen R (2001) Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical conse-quences // Am J Pharmacogenomics. – 2001. – Vol 1. – No3. – PP. 189–201.
15. Bae J, Shin SJ, Cha SH. et al (2007) Prevalent genotypes of methylenetetrahydrofolatereductase (MTHFR C677T and A1298C) inspontaneously aborted embryos, Fertility and Sterility, Vol. 87, No 2, рр. 351–355.
16. Engel SM, Olshan AF et al (2001) Polymorphisms in folate metabolizing genes and risk for spontaneous pre-term and small–for gestational age birth, Am. J. Obstet. Gynecol, Vol. 95, рр. 1231–1251.
17. Holmes ZR, Regan L, Chilcott I, Cohen H (1999) The C677T MTHFR gene mutation is not ppredictive of risk for recurrent fetal loss, Br. J. Haematol, Vol. 105, рр. 98–101.
18. Wu X, Zhao L, Zhu H et al (2012) Association between the MTHFR C677 Tppolymorpphism and recurrent ppregnancy loss: a meta–analysis, Genet Test Mol. Biomarkers, Vol. 16, No 7, рр. 806–811.
19. Botto L, Yang Q (2000) 5,10–Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a huge review, Am J Eppidemiol, Vol. 151, No 9, рр. 862–877.
20. Fodinger M, Horl W, Sunder–Plassmann G (1999) Molecular biology of 5,10–methylenetetrahydrofolate re-ductase, J. Nepphrol, No 13, рр. 1–17.
21. Wilcken B, Bamforth F, Li Z et al (2003) Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide, J. Med. Genet, Vol. 40, рр. 619–625.
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Kalimagambetоv A. M., Valyaeva, M. I., Isabek, A. U., Rakisheva, Z. B., Beysembaeva, S. A., Sadueva, K. A., & Dauletbaeva, S. B. (2018). Influence of folate cycle genes polymorphism on pregnancy complications in women of kazakh ethnic group. Experimental Biology, 70(1), 66–74. Retrieved from https://bb.kaznu.kz/index.php/biology/article/view/1253
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МOLECULAR BIOLOGY AND GENETICS
