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Apolipoprotein E polymorphism and silent microangiopathy-related cerebral damage. Results of the Austrian Stroke
R Schmidt1, H Schmidt, F Fazekas
1Department of Neurology, Karl-Franzens University Graz, Austria. reinhold.schmidt@kfunigraz.ac.at
Background And Purpose:
Microangiopathy-related cerebral damage (MARCD) includes white matter abnormalities and lacunar infarctions and represents a common MRI observation in subjects above 50 years of age. The risk factors of such brain abnormalities are not fully determined. The goal of this study was to determine whether the genetic heterogeneity of apolipoprotein E (apoE) contributes to the occurrence of MARCD.
Methods:
Brain MRI (1.5 T) was performed in 280 individuals (ages 50 to 75 years) without neuropsychiatric disease randomly selected from the official register of residents of the city of Graz, Austria. All study participants underwent apoE genotyping, carotid Doppler sonography, electrocardiography, echocardiography, and a complete blood chemistry panel. MARCD was defined as evidence of early confluent and confluent white matter hyperintensities or lacunes. Carotid atherosclerosis was graded on a five-point scale ranging from not present (0) to complete occlusion (5).
Results:
MARCD occurred in 61 individuals (21%). The distribution of apoE genotypes differed significantly between subjects with and without MARCD (P = .036). Subjects with such findings more commonly had the epsilon 2/epsilon 3 genotype (24.6% versus 10%) at similar frequencies of genotypes containing the epsilon 4 allele. The epsilon 2/epsilon 3 genotype was associated with lower levels of total cholesterol (P = .0009), LDL cholesterol (P = .00001), and apolipoprotein B (P = .00001). Also, there was a nonsignificant trend toward less cardiac disease. Other major vascular risk factors and carotid abnormalities were similar among the various genotypes. Multiple logistic regression analysis created a model of significant MARCD predictors, including age (odds ratio [OR], 1.1 per year), hypertension (OR, 3.4), and the apoE epsilon 2/epsilon 3 genotype (OR, 3.0).
Conclusions:
These data suggest an association between the apoE epsilon 2/epsilon 3 genotype and MARCD despite favorable effects on the lipid profile and cardiac disease.
Insights
The apolipoprotein E (apoE) epsilon 2/epsilon 3 genotype is linked to microangiopathy-related cerebral damage (MARCD) in individuals over 50. This association persists despite beneficial effects on cholesterol and cardiac health, highlighting a complex genetic influence on brain health.
Area of Science:
- Neuroimaging and Genetics
- Cerebrovascular Diseases
- Biomarkers
Background:
- Microangiopathy-related cerebral damage (MARCD) involves white matter abnormalities and lacunar infarctions, common in adults over 50.
- Risk factors for MARCD are not fully understood.
- Apolipoprotein E (apoE) genetic variations are investigated for their role in cerebrovascular health.
Purpose of the Study:
- To investigate the association between apolipoprotein E (apoE) genetic heterogeneity and the occurrence of MARCD.
- To determine if specific apoE genotypes contribute to the development of cerebral microangiopathy.
Main Methods:
- Brain MRI (1.5 T) was conducted on 280 individuals aged 50-75.
- Participants underwent apoE genotyping, carotid Doppler sonography, ECG, echocardiography, and blood chemistry analysis.
- MARCD was identified by white matter hyperintensities or lacunes on MRI.
Main Results:
- MARCD was present in 21% of participants.
- A significant difference in apoE genotype distribution was observed between subjects with and without MARCD (P = .036).
- The apoE epsilon 2/epsilon 3 genotype was associated with MARCD (OR, 3.0), lower LDL cholesterol, and apolipoprotein B levels.
Conclusions:
- The apoE epsilon 2/epsilon 3 genotype is associated with MARCD.
- This association exists even with favorable lipid profiles and reduced cardiac disease indicators.
- Age and hypertension are also significant predictors of MARCD.