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Genetic risk factors in young adults with 'cryptogenic' ischemic cerebrovascular disease
R Grossmann1, U Geisen, G Merati
1Central Laboratory and Blood Coagulation Unit of the Institute of Clinical Biochemistry and Pathobiochemistry, Würzburg, Germany. r.grossman@medizin.uni-wuerzburg.de
Insights
The factor V Leiden G1691A (FVL) mutation is a significant risk factor for cerebrovascular disease in young adults. Other mutations, including prothrombin G20210A (FIIM), did not show a contribution to risk in this patient group.
Area of Science:
- Genetics and Molecular Biology
- Neurology
- Cardiovascular Medicine
Background:
- Thromboembolism is a significant concern, particularly in young adults with unexplained cerebral ischemia.
- Several genetic mutations, including factor V Leiden G1691A (FVL) and prothrombin G20210A (FIIM), are known risk factors for thromboembolic events.
Purpose of the Study:
- To investigate the association between specific genetic mutations and the risk of cerebral ischemia in young adults (<50 years).
- To determine the role of FVL, FIIM, MTHFR C677T, CBS 844ins68, and EPCR 4031ins23 mutations in young adults with thromboembolic stroke or transient ischemic attacks.
Main Methods:
- A case-control study was conducted involving 93 young adult patients with cerebral ischemia and 186 healthy age- and sex-matched controls.
- Genotyping was performed to detect the presence of FVL, FIIM, MTHFR C677T, CBS 844ins68, and EPCR 4031ins23 mutations.
- Statistical analysis, including odds ratios (OR) and 95% confidence intervals (CI), was used to assess the risk associated with each mutation, with adjustments for smoking, hypertension, and hyperlipidemia.
Main Results:
- The FVL mutation was significantly associated with an increased risk of cerebral ischemia in young adults (OR, 3.19; 95% CI, 1.38-7.39) after adjusting for confounding factors.
- No significant association was found between FIIM, MTHFR TT677 genotype, or CBS 844ins68 mutation and the risk of cerebral ischemia in this population.
- The EPCR 4031ins23 mutation was rare, observed in only one patient and no controls, warranting further investigation.
Conclusions:
- The factor V Leiden G1691A (FVL) mutation is identified as a significant risk factor for cerebrovascular disease in younger adults.
- Prothrombin G20210A (FIIM), MTHFR TT677 genotype, and CBS 844ins68 mutation do not appear to contribute to the risk of cerebral ischemia in this age group.
- The EPCR 4031ins23 mutation's role in cerebrovascular events requires additional research due to its low prevalence.
Abstract:
Mutations such as factor V Leiden G1691A (FVL), prothrombin G20210A (FIIM), methylenetetrahydrofolate reductase (MTHFR) C677T, cystathionine beta-synthase (CBS) 844ins68 and endothelial cell protein C receptor (EPCR) 4031ins23 are risk factors for thromboembolism. To assess the role of these mutations in young adults with cerebral ischemia of otherwise undetermined etiology, 93 patients younger than 50 years old with thromboembolic strokes or transient ischemic attacks were studied. One hundred and eighty-six healthy age-matched and sex-matched blood donors served as controls. The FVL mutation was detected in 15/93 patients and 13/186 controls. After adjustment for smoking, arterial hypertension, and hyperlipidemia, the association of the FVL mutation with cerebral ischemia [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.38-7.39] remained significant. One of 93 patients and 6/186 controls were carriers of FIIM (OR, 0.33; 95% CI, 0.04-2.75). We detected the MTHFR TT677 genotype in 9/93 patients and 26/186 controls (OR, 0.66; 95% CI, 0.30-1.47), a CBS 844ins68 mutation in 12/93 patients and 19/186 controls (OR, 1.30; 95% CI, 0.60-2.81), and an EPCR 4031ins23 mutation in 1/93 patients and in no control individual (P = 0.33). In conclusion, in younger adults the FVL mutation is a risk factor for cerebrovascular disease. FIIM, the MTHFR TT677 genotype and the CBS 844ins68 mutation did not contribute to the risk in this group of patients. The EPCR 4031ins23 mutation is very rare, its possible role needs further investigation.