Analysis of association between FGB, MTHFR, MTR and MTRR genes polymorphisms and ischemic and hemorrhagic stroke

Authors

DOI:

https://doi.org/10.14739/2310-1210.2020.4.208354

Keywords:

genetic polymorphism, stroke, risk factors

Abstract

 

The genetic component is a leading factor of stroke manifestation. Contribution of single nucleotide polymorphisms or combined genotypes to disease development has population differences. Special attention should be paid to genetic features in different types of strokes among the Ukrainian population.

The aim of the study was to estimate the association of polymorphisms between FGB, MTHFR, MTR, MTRR genes or gene-gene interaction and a risk of atherotrombotic ischemic stroke and intracranial hemorrhagic stroke among Ukrainians.

Materials and methods. 102 patients with atherotrombotic ischemic stroke, 56 patients with intracranial hemorrhagic stroke and 102 healthy control subjects were included in the study. The control group comprised peoples without cardiovascular diseases, family history of stroke and with normal lipid profile values. The mean age was 53.4 ± 9.1 years for stroke patients and 54.5 ± 8.2 years for the control group. Single nucleotide polymorphisms С677T (rs1801133) MTHFR gene, A66G (rs1801394) MTRR gene, A2756G (rs 1805087) MTR gene, C-148T (rs 1800787) FGB gene were detected by polymerase chain reaction (PCR) followed by restriction of amplificated fragments and polymorphism A1298C (rs1801131) MTHFR gene was determined by allele specific PCR method.

Results. The association between 1298СС genotype MTHFR gene (OR = 3.457, 95 % CI:1.053–11.357) and -148СТ genotype FGB gene (OR = 2.276, 95 % CI: 1.248–4.152) and a risk of atherotrombotic ischemic stroke was revealed. A risk of intracranial hemorrhagic stroke was associated with 66AG (OR = 2.643, 95 % CI: 1.059–6.593) and 66GG (OR = 4.826, 95 % CI: 1.858–12.535) genotypes of MTRR gene. Synergistic effect was shown for polymorphic loci of FGB/С-148Т and MTRR/A66G in atherotrombotic ischemic stroke development as well as independent effect of MTRR/A66G for intracranial hemorrhagic stroke.

Conclusions. There are some differences in the genetic components of different types of acute stroke in Ukrainians that should be taken into account when initiating therapy or preventative measures.

 

References

Murthy, P. S., Ashok, A., & Kiran, J. (2016). Plasma Fibrinogen Levels in Acute Stroke in Tertiary Care Hospital, Warangal. International journal of scientific study, 4(5), 50-54.

Maliarchuk, I. V., Gorovenko, N. G., Babochkina, A. R., & Osypenko, N. S. (2014). Doslidzhennia vplyvu polimorfnoho varianta S148T hena β-lantsiuha fibrynohenu na rezhym dozuvannia varfarynu [Investigation of the influence of C148T polymorphism of fibrinogen beta-chain gene on warfarin dosing]. Krovoobih ta hemostaz, (1-2), 115-118. [in Ukrainian].

Moore, J. H. (2010). Detecting, characterizing, and interpreting nonlinear gene-gene interactions using multifactor dimensionality reduction. Advances in genetics, 72, 101-116. https://doi.org/10.1016/B978-0-12-380862-2.00005-9

Rossokha, Z. I., Kyriachenko, S. P., & Gorovenko, N. G. (2018). Porivnialna otsinka modelei henetychnoho ryzyku reproduktyvnykh rozladiv, zumovlenykh polimorfizmom heniv MTHFR, MTRR, MTR1 [Comparative evaluation of genetic risk models of reproductive disorders caused by MTHFR, MTRR, MTR1 gene polymorphism]. Medychni perspektyvy, 23(2), 85-91. https://doi.org/10.26641/2307-0404.2018.2.133943 [in Ukrainian].

Wypasek, E., Stepien, E., Kot, M., Plicner, D., Kapelak, B., Sadowski, J., & Undas, A. (2012). Fibrinogen beta-chain -C148T polymorphism is associated with increased fibrinogen, C-reactive protein, and interleukin-6 in patients undergoing coronary artery bypass grafting. Inflammation, 35(2), 429-435. https://doi.org/10.1007/s10753-011-9332-6

Verschuur, M., de Jong, M., Felida, L., de Maat, M. P., & Vos, H. L. (2005). A hepatocyte nuclear factor-3 site in the fibrinogen beta promoter is important for interleukin 6-induced expression, and its activity is influenced by the adjacent -148C/T polymorphism. The Journal of biological chemistry, 280(17), 16763-16771. https://doi.org/10.1074/jbc.M501973200

Baranova, Ye. V. (2014). Marker vospaleniya u bol'nykh s razlichnymi tipami mozgovykh insul'tov [Marker of inflammation in patients with different types of cerebral strokes]. Mizhnarodnyi nevrolohichnyi zhurnal, (5), 45-48. [in Russian].

Kalinin, R. E., Suchkov, I. A., Rudakova, I. N., & Nikiforov, A. A. (2016). Vliyanie geneticheskikh faktorov na techenie posttromboticheskogo sindroma nizhnikh konechnostei [Influence of Genetic Factors on the Course of Postthrombotic Syndrome of the Lower Limbs]. Novosti Khirurgii, 24(2), 125-130. https://doi.org/10.18484/2305-0047.2016.2.125 [in Russian].

Ganguly, P., & Alam, S. F. (2015). Role of homocysteine in the development of cardiovascular disease. Nutrition journal, 14, Article 6. https://doi.org/10.1186/1475-2891-14-6

Lin, Z., Li, Q., Sun, Y., Huang, J., Wang, W., Fu, J., Xu, J., & Zeng, D. (2019). Interactions between genetic variants involved in the folate metabolic pathway and serum lipid, homocysteine levels on the risk of recurrent spontaneous abortion. Lipids in health and disease, 18(1), Article 143. https://doi.org/10.1186/s12944-019-1083-7

Borovkova, E. I., Antipova, N. V., Korneenko, T. V., Shakhparonov, M. I., & Borovkov, I. M. (2017). Paraoksonaza: universal'nyi faktor antioksidantnoi zashchity organizma cheloveka [Paraoxonase: The Universal Factor of Antioxidant Defense in Human Body]. Vestnik RAMN, 72(1), 5-10. https://doi.org/10.15690/vramn764 [in Russian].

Wu, X., Xu, W., Zhou, T., Cao, N., Ni, J., Zou, T., Liang, Z., Wang, X., & Fenech, M. (2016). The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene-Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients. International journal of molecular sciences, 17(7), Article 1003. https://doi.org/10.3390/ijms17071003

Dmytruk, I. M., Makukh, H. V., Thyrkus, M. Y., & Kitsera N. I. (2016). The polymorphisms of genes involved in DNA methylation in patients with malignancies from West Ukraine. Вiopolymers and Cell, 32(4), 279-288. http://dx.doi.org/10.7124/bc.00092A

Wu, B., Liu, K., Yang, J. P., Hu, Y., Zhang, J., & He, J. X. (2017). The association between methionine synthase A2756G polymorphism and hematological cancer: A meta-analysis. Medicine, 96(48), Article e7469. https://doi.org/10.1097/MD.0000000000007469

Kalani, A., Chaturvedi, P., Kalani, K., Kamat, P. K., & Chaturvedi, P. (2019). A high methionine, low folate and vitamin B6/B12 containing diet can be associated with memory loss by epigenetic silencing of netrin-1. Neural regeneration research, 14(7), 1247-1254. https://doi.org/10.4103/1673-5374.251333

How to Cite

1.
Tsymbaliuk VI, Vasylieva IG, Kostiuk MR, Chopyk NG, Galanta OS, Tsiubko OI, Oleksenko NP, Dmytrenko AB, Makarova TA, Snitzar ND. Analysis of association between FGB, MTHFR, MTR and MTRR genes polymorphisms and ischemic and hemorrhagic stroke. Zaporozhye Medical Journal [Internet]. 2020Jul.22 [cited 2024Nov.23];22(4). Available from: http://zmj.zsmu.edu.ua/article/view/208354

Issue

Section

Original research