Evaluation of the interactions of common genetic mutations in stroke subtypes

• Published in: Journal of neurology Vol. 249; no. 10; pp. 1391 - 1397
• Main Authors: SZOLNOKI, Zoltan, SOMOGYVARI, Ferenc, KONDACS, Andras, SZABO, Mihaly, FODOR, Lajos
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.10.2002; Springer Nature B.V
• Subjects: Adult; Aged; Apolipoproteins E - genetics; Biological and medical sciences; Brain Ischemia - genetics; Factor V - genetics; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Neurology; Oxidoreductases Acting on CH-NH Group Donors - genetics; Peptidyl-Dipeptidase A - genetics; Polymerase Chain Reaction; Prothrombin - genetics; Risk Factors; Stroke - classification; Stroke - genetics; Vascular diseases and vascular malformations of the nervous system; Vascular disease; Human; Nervous system diseases; Stroke; Central nervous system disease; Risk factor; Cardiovascular disease; Genetics; Mutation; Subtype; Cerebrovascular disease; Cerebral disorder
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-002-0848-4

Ischemic stroke is a frequent heterogeneous multifactorial disease that is affected by several genetic mutations and environmental factors. We hypothesised the clinical importance of the co-occurrence of common, unfavorable genetic mutations in the development of different stroke subtypes. The Factor V Leiden G1691A (Leiden V), the prothrombin G20210A and the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations and the angiotensin-converting enzyme I/D (ACE I/D) and apolipoprotein E (APOE) genotypes were examined by the PCR technique in 689 ischemic stroke patients and 652 stroke-free controls. Logistic regression models were used to estimate the relative risks of different stroke subtypes for different genotype combination patterns. The ACE D/D genotype alone or in combination with the MTHFR 677T or the APOE 4 allele or with both was highly specific for small-vessel infarction. The Leiden V mutation alone or in different combination patterns with the ACE D, APOE 4 and MTHFR 677T alleles was specifically predisposed to large-vessel infarction. The APOE 4 allele alone was calculated to be a general, minor genetic risk factor for ischemic stroke. The MTHFR 677T allele alone was not a risk factor for any stroke subtype. In the different specific predisposition gene combinations, however, both the APOE 4 and MTHFR 677T alleles could increase the relative risk of the given stroke subgroup. Common mutations which alone are minor or non-significant risk factors for ischemic stroke can yield, in specific combination patterns, a highly significant, moderate genetic risk of specific stroke subtypes.