Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population

M Schuur, J C van Swieten, S Schol-Gelok, M A Ikram, M W Vernooij, F Liu, A Isaacs, R de Boer, I de Koning, W J Niessen, H Vrooman, B A Oostra, A van der Lugt, M M B Breteler, C M van Duijn

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 languageEnglish
Pages (from-to)41-4
Number of pages4
JournalJournal of Neurology Neurosurgery and Psychiatry
Volume82
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Keywords

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

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