title: Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population.
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.
  
  
  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).
  
  
  CONCLUSIONS
  The association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.
authors.affiliation: Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schuur
authors.forename: J C
authors.initials: JC
authors.lastname: van Swieten
authors.forename: S
authors.initials: S
authors.lastname: Schol-Gelok
authors.forename: M A
authors.initials: MA
authors.lastname: Ikram
authors.forename: M W
authors.initials: MW
authors.lastname: Vernooij
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Isaacs
authors.forename: R
authors.initials: R
authors.lastname: de Boer
authors.forename: I
authors.initials: I
authors.lastname: de Koning
authors.forename: W J
authors.initials: WJ
authors.lastname: Niessen
authors.forename: H
authors.initials: H
authors.lastname: Vrooman
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: A
authors.initials: A
authors.lastname: van der Lugt
authors.forename: M M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000368:Aged; D000682:Amyloid / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001794:Blood Pressure / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D000099291:Adducins
chemical_list: D000682:Amyloid; D001057:Apolipoproteins E; D002148:Calmodulin-Binding Proteins; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D044140:Receptor, Angiotensin, Type 1; D000099291:Adducins; C102582:SORL1 protein, human