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PAPER |
1 Department of Neurology and Neurophysiology, Pándy Kálmán County Hospital, Gyula, Hungary
2 Central Laboratory, Pándy Kálmán County Hospital, Gyula, Hungary
3 MTA-PTE Clinical Genetics Research Group of Hungarian Academy of Sciences, Department of Medical Genetics and Child Development, University of Pécs, Hungary
Correspondence to:
Correspondence to:
Dr Z Szolnoki
H-5600 Békéscsaba, Pipacs köz 9, Hungary; szolnoki99{at}hotmail.com
Methods: The Factor V Leiden G1691A (Leiden V), the prothrombin G20210A, the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations, the angiotensin converting enzyme I/D (ACE I/D), and apolipoprotein allele e4 (APO e4) genotypes were examined by the polymerase chain reaction (PCR) technique in 867 ischaemic stroke patients and 743 healthy controls. Logistic regression models were used to estimate the roles of the co-occurrences of the clinical risk factors and common genetic mutations in ischaemic stroke.
Results: The Leiden V mutation in combination with hypertension or diabetes mellitus increased the risk of ischaemic stroke. We found synergistic effects between the ACE D/D and MTHFR 677TT genotypes and drinking or smoking. The presence of the APO e4 greatly facilitated the unfavourable effects of hypertension, diabetes mellitus, smoking, or drinking on the incidence of ischaemic stroke.
Conclusion: In certain combinations, pairing of common unfavourable genetic factors, which alone confer only minor or non-significant risk, with clinical risk factors can greatly increase the susceptibility to ischaemic stroke.
Keywords: genetics; interactions; modifying effect
Abbreviations: ACE, angiotensin converting enzyme; PCR, polymerase chain reaction; MRI, magnetic resonance imaging; CT, computerised tomography; TIA, transient ischaemic attack; EGC, electrocardiogram; BMI, body mass index; EDTA, ethylene diamine tetra-acetic acid; OR, odds ratio; CI, confidence interval
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