Альманах клинической медицины. 2018; 46: 254-257
Изучение связи полиморфизма rs1801133 гена MTHFR c дефицитом фолиевой кислоты у больных ожирением
https://doi.org/10.18786/2072-0505-2018-46-3-254-257Аннотация
Актуальность. Применение молекулярно-генетических технологий позволило показать, что в развитии ожирения существенную роль играет генетический фактор. Кроме того, у людей, страдающих ожирением, обеспеченность витаминами, в частности фолиевой кислотой, в значительной степени контролируется генетически.
Цель – изучить ассоциации полиморфизма rs1801133 гена MTHFR c обеспеченностью фолиевой кислотой в зависимости от индекса массы тела у жителей Московского региона.
Материал и методы. Идентификация полиморфизмов rs1801133 проведена у 326 человек (74 мужчины и 252 женщины) в возрасте от 20 до 65 лет, проживающих в Московском регионе. ДНК выделяли из крови методом сорбции на магнитные частицы, покрытые силикагелем. Процесс выделения ДНК осуществляли на автоматической станции epMotion 5075 (“Eppendorf”, Германия). Для идентификации полиморфизма применяли полимеразную цепную реакцию с последующим расщеплением продуктов амплификации рестриктазой Hinf1 и анализом этих продуктов методом гель-электрофореза. Использовали оборудование CFX96 Real Time System (“Bio-Rad”, США). Фолиевую кислоту определяли с использованием тест-системы ID-Vit® Folic acid (“R-Biopharm”, Германия).
Результаты. По данным определения уровня фолиевой кислоты в крови, у 24,2% обследованных жителей Московского региона наблюдался дефицит этого витамина. Анализ результатов генотипирования не установил наличие связи полиморфизма rs1801133 гена MTHFR с уровнем фолиевой кислоты в сыворотке крови. Однако у людей с избыточной массой тела и ожирением выявлена статистически значимая ассоциация между аллелем Т полиморфизма rs1801133 гена MTHFR и низким уровнем фолиевой кислоты (отношение шансов 2,5, 95% доверительный интервал 1,09–5,74, р = 0,03).
Заключение. Полиморфизм rs1801133 гена MTHFR вносит существенный вклад в развитие дефицита фолиевой кислоты у людей с избыточной массой тела и ожирением.
Список литературы
1. Thomas-Valdés S, Tostes MDGV, Anunciação PC, da Silva BP, Sant'Ana HMP. Association between vitamin deficiency and metabolic disorders related to obesity. Crit Rev Food Sci Nutr. 2017;57(15): 3332–43. doi: 10.1080/10408398.2015.1117413.
2. Liu X, Zhao LJ, Liu YJ, Xiong DH, Recker RR, Deng HW. The MTHFR gene polymorphism is associated with lean body mass but not fatbody mass. Hum Genet. 2008;123(2): 189–96. doi: 10.1007/s00439-007-0463-7.
3. Tavakkoly Bazzaz J, Shojapoor M, Nazem H, Amiri P, Fakhrzadeh H, Heshmat R, Parvizi M, Hasani Ranjbar S, Amoli MM. Methylenetetrahydrofolate reductase gene polymorphism in diabetes and obesity. Mol Biol Rep. 2010;37(1): 105–9. doi: 10.1007/s11033-009-9545-z.
4. Binia A, Contreras AV, Canizales-Quinteros S, Alonzo VA, Tejero ME, Silva-Zolezzi I. Geographical and ethnic distribution of single nucleotide polymorphisms within genes of the folate/homocysteine pathway metabolism. Genes Nutr. 2014;9(5): 421. doi: 10.1007/s12263-014-0421-7.
5. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF 3rd, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, Molloy AM, Caudill MA, Shane B, Berry RJ, Bailey RL, Hausman DB, Raghavan R, Raiten DJ. Biomarkers of Nutrition for Development – Folate Review. J Nutr. 2015;145(7): 1636S–80S. doi: 10.3945/jn.114.206599.
6. Sun J, Xu Y, Xue J, Zhu Y, Lu H. Methylenetetrahydrofolate reductase polymorphism associated with susceptibility to coronary heart disease in Chinese type 2 diabetic patients. Mol Cell Endocrinol. 2005;229(1–2): 95–101. doi: 10.1016/j.mce.2004.09.003.
7. Zhu B, Wu X, Zhi X, Liu L, Zheng Q, Sun G. Methylenetetrahydrofolate reductase C677T polymorphism and type 2 diabetes mellitus in Chinese population: a meta-analysis of 29 case-control studies. PLoS One. 2014;9(7):e102443. doi: 10.1371/journal.pone.0102443.
8. Movva S, Alluri RV, Venkatasubramanian S, Vedicherla B, Vattam KK, Ahuja YR, Hasan Q. Association of methylene tetrahydrofolate reductase C677T genotype with type 2 diabetes mellitus patients with and without renal complications. Genet Test Mol Biomarkers. 2011;15(4): 257–61. doi: 10.1089/gtmb.2010.0118.
9. Raza ST, Abbas S, Siddiqi Z, Mahdi F. Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia. Int J Mol Cell Med. 2017;6(2): 121–30. doi: 10.22088/acadpub.BUMS.6.2.6.
10. Karic A, Terzic R, Jerkic Z, Mustedanagic-Mujanovic J. The frequency of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism in Southern East Bosnian population. J Biomet Biostat. 2013;4(4): 1000169. doi: 10.4172/2155-6180.1000169.
Almanac of Clinical Medicine. 2018; 46: 254-257
Evaluation of an association of the rs1801133 MTHFR gene polymorphism with folic acid deficiency in obese patients
https://doi.org/10.18786/2072-0505-2018-46-3-254-257Abstract
Background: The use of molecular genetic technologies has made it possible to show that the genetic factor plays a significant role in the development of obesity. In addition, in obese people the supply with vitamins, in particular with folic acid, is largely controlled genetically.
Aim: To study an association of the rs1801133 polymorphism of the MTHFR gene with folic acid deficiency in the residents of the Moscow region depending on their body mass index.
Materials and methods: rs1801133 polymorphisms were identified in 326 subjects (74 male and 252 female) aged from 20 to 65 years, living in the Moscow region. The DNA was isolated from blood by the sorption on silica gel-coated magnetic particles. DNA was isolated with the use of the epMotion 5075 automatic station (Eppendorf, Germany). To identify the polymorphism, a polymerase chain reaction was used, followed by cleavage of the Hinf1 restriction endonuclease products, with analysis of these products by gel electrophoresis. The equipment CFX96 Real Time System (BIO-RAD, USA) was used. Folic acid was measured by ID-Vit® Folic Acid test system (R-Biopharm, Germany).
Results: According to the results of folic acid measurements in blood, a deficiency of this vitamin was found in 24.2% of the studied residents of the Moscow region. Analysis of the genotyping results did not show any association of the rs1801133 MTHFR gene polymorphism with the serum levels of folic acid. However, in the subjects with overweight and obesity, there was a statistically significant association between the T allele of the rs1801133 of the MTHFR gene polymorphism and a low level of folic acid (odds ratio 2.5, 95% confidence interval 1.09–5.74, p = 0.03).
Conclusion: The rs1801133 polymorphism of the MTHFR gene significantly contributes to the development of folic acid deficiency in overweight and obese individuals.
References
1. Thomas-Valdés S, Tostes MDGV, Anunciação PC, da Silva BP, Sant'Ana HMP. Association between vitamin deficiency and metabolic disorders related to obesity. Crit Rev Food Sci Nutr. 2017;57(15): 3332–43. doi: 10.1080/10408398.2015.1117413.
2. Liu X, Zhao LJ, Liu YJ, Xiong DH, Recker RR, Deng HW. The MTHFR gene polymorphism is associated with lean body mass but not fatbody mass. Hum Genet. 2008;123(2): 189–96. doi: 10.1007/s00439-007-0463-7.
3. Tavakkoly Bazzaz J, Shojapoor M, Nazem H, Amiri P, Fakhrzadeh H, Heshmat R, Parvizi M, Hasani Ranjbar S, Amoli MM. Methylenetetrahydrofolate reductase gene polymorphism in diabetes and obesity. Mol Biol Rep. 2010;37(1): 105–9. doi: 10.1007/s11033-009-9545-z.
4. Binia A, Contreras AV, Canizales-Quinteros S, Alonzo VA, Tejero ME, Silva-Zolezzi I. Geographical and ethnic distribution of single nucleotide polymorphisms within genes of the folate/homocysteine pathway metabolism. Genes Nutr. 2014;9(5): 421. doi: 10.1007/s12263-014-0421-7.
5. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF 3rd, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, Molloy AM, Caudill MA, Shane B, Berry RJ, Bailey RL, Hausman DB, Raghavan R, Raiten DJ. Biomarkers of Nutrition for Development – Folate Review. J Nutr. 2015;145(7): 1636S–80S. doi: 10.3945/jn.114.206599.
6. Sun J, Xu Y, Xue J, Zhu Y, Lu H. Methylenetetrahydrofolate reductase polymorphism associated with susceptibility to coronary heart disease in Chinese type 2 diabetic patients. Mol Cell Endocrinol. 2005;229(1–2): 95–101. doi: 10.1016/j.mce.2004.09.003.
7. Zhu B, Wu X, Zhi X, Liu L, Zheng Q, Sun G. Methylenetetrahydrofolate reductase C677T polymorphism and type 2 diabetes mellitus in Chinese population: a meta-analysis of 29 case-control studies. PLoS One. 2014;9(7):e102443. doi: 10.1371/journal.pone.0102443.
8. Movva S, Alluri RV, Venkatasubramanian S, Vedicherla B, Vattam KK, Ahuja YR, Hasan Q. Association of methylene tetrahydrofolate reductase C677T genotype with type 2 diabetes mellitus patients with and without renal complications. Genet Test Mol Biomarkers. 2011;15(4): 257–61. doi: 10.1089/gtmb.2010.0118.
9. Raza ST, Abbas S, Siddiqi Z, Mahdi F. Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia. Int J Mol Cell Med. 2017;6(2): 121–30. doi: 10.22088/acadpub.BUMS.6.2.6.
10. Karic A, Terzic R, Jerkic Z, Mustedanagic-Mujanovic J. The frequency of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism in Southern East Bosnian population. J Biomet Biostat. 2013;4(4): 1000169. doi: 10.4172/2155-6180.1000169.
