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. 2020 Jul 24;10(8):476.
doi: 10.3390/brainsci10080476.

MTHFR Gene Polymorphisms Prevalence and Cardiovascular Risk Factors Involved in Cardioembolic Stroke Type and Severity

Dana Simona Chita  1   2 , Anca Tudor  3 , Ruxandra Christodorescu  4 , Florina Nicoleta Buleu  2 , Raluca Sosdean  2   5 , Sanda Maria Deme  1 , Simona Mercea  6 , Adina Pop Moldovan  6 , Ana Maria Pah  2   5 , Any Docu Axelerad  7 , Daniel Docu Axelerad  8 , Simona Ruxanda Dragan  2   5
Affiliations

MTHFR Gene Polymorphisms Prevalence and Cardiovascular Risk Factors Involved in Cardioembolic Stroke Type and Severity

Dana Simona Chita et al. Brain Sci. .

Abstract

Background: Cardioembolic stroke (CES), generally known as the most severe subtype of ischemic stroke, is related to many factors, including diabetes mellitus (DM), hypertension (HTN), smoking, hyperlipidemia and atrial fibrillation (AF). Genetic mutations of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C have been recently associated with ischemic stroke. The purpose of this study was to analyze the prevalence of MTHFR gene polymorphisms correlated with cardiovascular risk factors in a selected population of patients with CES due to non-valvular AF (NVAF).

Methods: This cross-sectional study was performed on 67 consecutive patients with acute cardioembolic stroke admitted to our hospital. The protocol included general physical examination, neurological clinical status and stroke severity evaluation, imagistic evaluation and genetic testing of MTHFRC677T and A1298C polymorphisms.

Results: The prevalence of MTHFR polymorphisms in the study population was 38.2% for C677T and 40.3% for A1298C. The C677T mutation was significantly correlated with increased diastolic blood pressure (DBP) values (p = 0.007), higher total cholesterol (TC) (p = 0.003), low-density lipoprotein cholesterol (LDLc) (p = 0.003) and triglycerides (TGL) (p = 0.001), increased high-sensitive C-reactive protein (hsCRP) values (p = 0.015), HbA1c (p = 0.004) and left ventricle ejection fraction (LVEF) (p = 0.047) and lower high-density lipoprotein cholesterol (HDLc) (p < 0.001) compared to patients without this genetic variant. This genetic profile also included significantly higher CHA2DS2VASC (p = 0.029) and HASBLED (Hypertension, Abnormal liver/renal function, Stroke, Bleeding, Labile INR, Elderly age(>65 years), Drug/Alcohol usage history/Medication usage with bleeding predisposition) (p = 0.025) scores. Stroke severity in patients with MTHFRA1298C mutation was significantly increased when applying National Institutes of Health Stroke Scale (NIHSS) (p = 0.006) and modified Rankin scale (mRS) (p = 0.020) scores. The presence of A1298C mutation as a dependent variable was associated with significantly higher TGL values (odds ratio (OR) = 2.983, 95%CI = (1.972, 7.994)).

Conclusions: The results obtained in this study demonstrate that MTHFR gene polymorphisms have a high prevalence in an NVAF cardioembolic stroke population. Moreover, an association between C677T mutation and stroke severity was highlighted. The C677T mutation in patients with NVAF was correlated with a higher incidence of cardiovascular comorbidities (hypertension HTN, heart failure (HF), dyslipidemia, type II diabetes mellitus (T2DM) with high HbA1c and increased inflammatory state). The A1298CMTHFR gene mutation was associated with a higher incidence of previous lacunar stroke and stroke recurrence rate, while dyslipidemia was the main cardiovascular comorbidity in this category.

Keywords: A1298C mutation; C677T mutation; MTHFR gene polymorphisms; cardioembolic stroke; non-valvular atrial fibrillation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patients with C677T mutation have a higher risk for developing higher DBP values (odds ratio (OR) = 1.881, 95%CI = (1.804, 4.964)).
Figure 2
Figure 2
Patients with MTHFR C677T mutation have a high risk for increased HbA1c values (OR = 1.982, 95%CI = (1.171, 7.799)).
Figure 3
Figure 3
C677T mutation in the MTHFR gene is associated with a high risk for hypertrygliceridemia (OR = 1.392, 95%CI = (1.192, 3.994)).
Figure 4
Figure 4
MTHFR A1298C is associated with a risk for high triglycerides (TGL) values (OR = 2.983, 95%CI = (1.972, 7.994)).
Figure 5
Figure 5
Percentage of patients on acenocumarol vs. NOAC.
Figure 6
Figure 6
Association between cardioembolic stroke localization and MTHFR polymorphism by applying Chi2 Test.
Figure 7
Figure 7
Association between previous lacunar stroke and MTHFR polymorphisms using Chi2 Test.
Figure 8
Figure 8
Association between recurrent stroke and MTHFR polymorphisms by Chi2 Test.
Figure 9
Figure 9
Comparison of NIHSS scores between patients without vs. with one or both MTHFR polymorphisms.
Figure 10
Figure 10
Comparison between patients without vs. with one or both polymorphisms of the MTHFR gene regarding mRS scores.
See this image and copyright information in PMC

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References

    1. Donkor E.S. Stroke in the21stCentury: A snapshot of the burden, epidemiology, and quality of life. Stroke Res. Treat. 2018;2018 doi: 10.1155/2018/3238165. - DOI - PMC - PubMed
    1. Yiin G.S.C., Howard D.P.J., Paul N.L.M., Li L., Luengo-Fernandez R., Bull L.M., Welch S.J.V., Gutnikov S.A., Mehta Z., Rothwell P.M. Age-specific incidence, outcome, cost, and projected future burden of atrial fibrillation related embolic vascular events. Circulation. 2014;130:1236–1244. doi: 10.1161/CIRCULATIONAHA.114.010942. - DOI - PMC - PubMed
    1. Le T.Q.H., Nguyen V.T., Nguyen T.K., Phan H.T. 1162: Echocardiography and cardioembolic stroke. Ultrasound Med. Boil. 2009;35:S143. doi: 10.1016/j.ultrasmedbio.2009.06.545. - DOI
    1. Arboix A., Alió J. Cardioembolic stroke: Clinical features, specific cardiac disorders and prognosis. Curr. Cardiol. Rev. 2010;6:150–161. doi: 10.2174/157340310791658730. - DOI - PMC - PubMed
    1. Kim J.O., Park H.S., Ryu C.S., Shin J.-W., Kim J., Oh S.H., Kim O.J., Kim N.K. Interplay between 3′-UTR polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the risk of ischemic stroke. Sci. Rep. 2017;7:12464. doi: 10.1038/s41598-017-12668-x. - DOI - PMC - PubMed