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

Maaike Schuur, J.C. van Swieten, S Schol-Gelok, Arfan Ikram, Meike Vernooij, Fan Liu, Aaron Isaacs, Renske Boer, I Koning, Wiro Niessen, Henri Vrooman, Ben Oostra, Aad van der Lugt, Monique Breteler, Cornelia Duijn

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)

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, alpha-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 epsilon 4 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)41-44
Number of pages4
JournalJournal of Neurology Neurosurgery and Psychiatry
Volume82
Issue number1
DOIs
Publication statusPublished - 2011

Fingerprint

Dive into the research topics of 'Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population'. Together they form a unique fingerprint.

Cite this