<i>MTHFR</i> Gene Polymorphisms Prevalence and Cardiovascular Risk Factors Involved in Cardioembolic Stroke Type and Severity

• Main Authors: Dana Simona Chita, Anca Tudor, Ruxandra Christodorescu, Florina Nicoleta Buleu, Raluca Sosdean, Sanda Maria Deme, Simona Mercea, Adina Pop Moldovan, Ana Maria Pah, Any Docu Axelerad, Daniel Docu Axelerad, Simona Ruxanda Dragan
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Brain Sciences
• Subjects: cardioembolic stroke; <i>MTHFR</i> gene polymorphisms; <i>C677T</i> mutation; <i>A1298C</i> mutation; non-valvular atrial fibrillation
• Online Access: https://www.mdpi.com/2076-3425/10/8/476

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 <em>(</em><em>MTHFR</em><em>)</em> gene <em>C677T</em> and <em>A1298C</em> have been recently associated with ischemic stroke. The purpose of this study was to analyze the prevalence of <em>MTHFR</em> 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 <em>MTHFR</em> <em>C677T</em> and <em>A1298C</em> polymorphisms. Results: The prevalence of <em>MTHFR</em> polymorphisms in the study population was 38.2% for <em>C677T</em> and 40.3% for <em>A1298C</em>. The <em>C677T</em> mutation was significantly correlated with increased diastolic blood pressure (DBP) values (<em>p </em>= 0.007), higher total cholesterol (TC) (<em>p </em>= 0.003), low-density lipoprotein cholesterol (LDLc) (<em>p </em>= 0.003) and triglycerides (TGL) (<em>p </em>= 0.001), increased  high-sensitive C-reactive protein (hsCRP) values (<em>p </em>= 0.015), HbA1c (<em>p </em>= 0.004) and left ventricle ejection fraction (LVEF) (<em>p </em>= 0.047) and lower high-density lipoprotein cholesterol (HDLc) (<em>p </em>< 0.001) compared to patients without this genetic variant. This genetic profile also included significantly higher CHA₂DS₂VASC (<em>p </em>= 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) (<em>p </em>= 0.025) scores. Stroke severity in patients with <em>MTHFR</em> <em>A1298C</em> mutation was significantly increased when applying National Institutes of Health Stroke Scale (NIHSS) (<em>p </em>= 0.006) and modified Rankin scale (mRS) (<em>p </em>= 0.020) scores. The presence of <em>A1298C</em> 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 <em>MTHFR</em> gene polymorphisms have a high prevalence in an NVAF cardioembolic stroke population. Moreover, an association between <em>C677T</em> mutation and stroke severity was highlighted. The <em>C677T</em> 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 <em>A1298C</em> <em>MTHFR</em> 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.