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BACKGROUND: Asymptomatic cerebral lesions on MRI such as white matter lesions (WML), lacunes and microbleeds are commonly seen in older people. We examined the role of a series of candidate genes involved in blood pressure regulation and amyloid metabolism. MATERIALS AND METHODS: The study was embedded in a family-based cohort sampled from a Dutch genetically isolated population. We selected individuals between 55 and 75 years of age with hypertension (N=129). Volumes of WML and presence of lacunes and microbleeds were assessed with MRI. We studied three genes involved in blood pressure regulation (angiotensin, angiotensin II type 1 receptor, α-adducin) and two genes involved in the amyloid pathway (apolipoprotein E (APOE) and sortilin-related receptor gene (SORL1)). RESULTS: All participants had WML (median volume, 3.1 ml; interquartile range, 1.5-6.5 ml); lacunar infarcts were present in 15.5% and microbleeds in 23.3%. Homozygosity for the APOE ε4 allele was associated with lacunes (OR, 4.8; 95% CI, 1.2 to 19.3). Individuals carrying two copies of the variant allele of four single nucleotide polymorphism (SNPs) located at the 3'-end of SORL1 (rs1699102, rs3824968, rs2282649, rs1010159) had significantly more often microbleeds (highest OR, 6.87; 95% CI, 1.78 to 26.44). CONCLUSION: The association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.

Original publication

DOI

10.1136/jnnp.2009.176362

Type

Journal article

Journal

J Neurol Neurosurg Psychiatry

Publication Date

01/2011

Volume

82

Pages

41 - 44

Keywords

Aged, Amyloid, Apolipoproteins E, Blood Pressure, Calmodulin-Binding Proteins, Cerebral Hemorrhage, Cerebrovascular Disorders, Cognition Disorders, Cohort Studies, Female, Genotype, Humans, Hypertension, LDL-Receptor Related Proteins, Magnetic Resonance Imaging, Male, Membrane Transport Proteins, Middle Aged, Netherlands, Neuropsychological Tests, Polymorphism, Single Nucleotide, Receptor, Angiotensin, Type 1