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

BackgroundAsymptomatic 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 MethodsThe study was embedded i... Full description

Journal Title: Journal of neurology neurosurgery and psychiatry, 2011-01, Vol.82 (1), p.41-44
Main Author: Schuur, M
Other Authors: van Swieten, J C , Schol-Gelok, S , Ikram, M A , Vernooij, M W , Liu, F , Isaacs, A , de Boer, R , de Koning, I , Niessen, W J , Vrooman, H , Oostra, B A , van der Lugt, A , Breteler, M M B , van Duijn, C M
Format: Electronic Article Electronic Article
Language: English
Subjects:
Age
RAS
Publisher: London: BMJ Publishing Group Ltd
ID: ISSN: 0022-3050
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title: Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population
format: Article
creator:
  • Schuur, M
  • van Swieten, J C
  • Schol-Gelok, S
  • Ikram, M A
  • Vernooij, M W
  • Liu, F
  • Isaacs, A
  • de Boer, R
  • de Koning, I
  • Niessen, W J
  • Vrooman, H
  • Oostra, B A
  • van der Lugt, A
  • Breteler, M M B
  • van Duijn, C M
subjects:
  • Age
  • Aged
  • Alzheimers disease
  • Amyloid - genetics
  • Amyloid - metabolism
  • APOE
  • Apolipoproteins
  • Apolipoproteins E - genetics
  • Atherosclerosis
  • Biological and medical sciences
  • Blood Pressure - physiology
  • Calmodulin-Binding Proteins - genetics
  • Cerebral Hemorrhage - etiology
  • Cerebral Hemorrhage - pathology
  • Cerebral small-vessel disease
  • Cerebrovascular disease
  • Cerebrovascular Disorders - epidemiology
  • Cerebrovascular Disorders - etiology
  • Cerebrovascular Disorders - genetics
  • Cholesterol
  • Cognition Disorders - etiology
  • Cognition Disorders - psychology
  • Cognitive ability
  • Cohort Studies
  • Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
  • Dementia
  • Demographic aspects
  • Female
  • Genes
  • Genetic aspects
  • Genotype
  • Haplotypes
  • Health risk assessment
  • Humans
  • Hypertension
  • Hypertension - complications
  • Hypertension - epidemiology
  • Hypertension - genetics
  • LDL-Receptor Related Proteins - genetics
  • Magnetic Resonance Imaging
  • Male
  • Medical sciences
  • Membrane Transport Proteins - genetics
  • microbleeds
  • Middle Aged
  • Netherlands - epidemiology
  • Neurology
  • Neuropsychological Tests
  • Pathogenesis
  • Polymorphism, Single Nucleotide - genetics
  • Population
  • RAS
  • Receptor, Angiotensin, Type 1 - genetics
  • Risk factors
  • SORL1
  • Studies
ispartof: Journal of neurology, neurosurgery and psychiatry, 2011-01, Vol.82 (1), p.41-44
description: BackgroundAsymptomatic 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 MethodsThe 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)).ResultsAll 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).ConclusionThe association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.
language: eng
source:
identifier: ISSN: 0022-3050
fulltext: no_fulltext
issn:
  • 0022-3050
  • 1468-330X
url: Link


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titleGenetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population
creatorSchuur, M ; van Swieten, J C ; Schol-Gelok, S ; Ikram, M A ; Vernooij, M W ; Liu, F ; Isaacs, A ; de Boer, R ; de Koning, I ; Niessen, W J ; Vrooman, H ; Oostra, B A ; van der Lugt, A ; Breteler, M M B ; van Duijn, C M
creatorcontribSchuur, M ; van Swieten, J C ; Schol-Gelok, S ; Ikram, M A ; Vernooij, M W ; Liu, F ; Isaacs, A ; de Boer, R ; de Koning, I ; Niessen, W J ; Vrooman, H ; Oostra, B A ; van der Lugt, A ; Breteler, M M B ; van Duijn, C M
descriptionBackgroundAsymptomatic 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 MethodsThe 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)).ResultsAll 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).ConclusionThe association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.
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languageeng
publisherLondon: BMJ Publishing Group Ltd
subjectAge ; Aged ; Alzheimers disease ; Amyloid - genetics ; Amyloid - metabolism ; APOE ; Apolipoproteins ; Apolipoproteins E - genetics ; Atherosclerosis ; Biological and medical sciences ; Blood Pressure - physiology ; Calmodulin-Binding Proteins - genetics ; Cerebral Hemorrhage - etiology ; Cerebral Hemorrhage - pathology ; Cerebral small-vessel disease ; Cerebrovascular disease ; Cerebrovascular Disorders - epidemiology ; Cerebrovascular Disorders - etiology ; Cerebrovascular Disorders - genetics ; Cholesterol ; Cognition Disorders - etiology ; Cognition Disorders - psychology ; Cognitive ability ; Cohort Studies ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Dementia ; Demographic aspects ; Female ; Genes ; Genetic aspects ; Genotype ; Haplotypes ; Health risk assessment ; Humans ; Hypertension ; Hypertension - complications ; Hypertension - epidemiology ; Hypertension - genetics ; LDL-Receptor Related Proteins - genetics ; Magnetic Resonance Imaging ; Male ; Medical sciences ; Membrane Transport Proteins - genetics ; microbleeds ; Middle Aged ; Netherlands - epidemiology ; Neurology ; Neuropsychological Tests ; Pathogenesis ; Polymorphism, Single Nucleotide - genetics ; Population ; RAS ; Receptor, Angiotensin, Type 1 - genetics ; Risk factors ; SORL1 ; Studies
ispartofJournal of neurology, neurosurgery and psychiatry, 2011-01, Vol.82 (1), p.41-44
rights
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0Schuur, M
1van Swieten, J C
2Schol-Gelok, S
3Ikram, M A
4Vernooij, M W
5Liu, F
6Isaacs, A
7de Boer, R
8de Koning, I
9Niessen, W J
10Vrooman, H
11Oostra, B A
12van der Lugt, A
13Breteler, M M B
14van Duijn, C M
title
0Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population
1Journal of neurology, neurosurgery and psychiatry
addtitleJ Neurol Neurosurg Psychiatry
descriptionBackgroundAsymptomatic 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 MethodsThe 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)).ResultsAll 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).ConclusionThe association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.
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0Age
1Aged
2Alzheimers disease
3Amyloid - genetics
4Amyloid - metabolism
5APOE
6Apolipoproteins
7Apolipoproteins E - genetics
8Atherosclerosis
9Biological and medical sciences
10Blood Pressure - physiology
11Calmodulin-Binding Proteins - genetics
12Cerebral Hemorrhage - etiology
13Cerebral Hemorrhage - pathology
14Cerebral small-vessel disease
15Cerebrovascular disease
16Cerebrovascular Disorders - epidemiology
17Cerebrovascular Disorders - etiology
18Cerebrovascular Disorders - genetics
19Cholesterol
20Cognition Disorders - etiology
21Cognition Disorders - psychology
22Cognitive ability
23Cohort Studies
24Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
25Dementia
26Demographic aspects
27Female
28Genes
29Genetic aspects
30Genotype
31Haplotypes
32Health risk assessment
33Humans
34Hypertension
35Hypertension - complications
36Hypertension - epidemiology
37Hypertension - genetics
38LDL-Receptor Related Proteins - genetics
39Magnetic Resonance Imaging
40Male
41Medical sciences
42Membrane Transport Proteins - genetics
43microbleeds
44Middle Aged
45Netherlands - epidemiology
46Neurology
47Neuropsychological Tests
48Pathogenesis
49Polymorphism, Single Nucleotide - genetics
50Population
51RAS
52Receptor, Angiotensin, Type 1 - genetics
53Risk factors
54SORL1
55Studies
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1van Swieten, J C
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3Ikram, M A
4Vernooij, M W
5Liu, F
6Isaacs, A
7de Boer, R
8de Koning, I
9Niessen, W J
10Vrooman, H
11Oostra, B A
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titleGenetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population
authorSchuur, M ; van Swieten, J C ; Schol-Gelok, S ; Ikram, M A ; Vernooij, M W ; Liu, F ; Isaacs, A ; de Boer, R ; de Koning, I ; Niessen, W J ; Vrooman, H ; Oostra, B A ; van der Lugt, A ; Breteler, M M B ; van Duijn, C M
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0Age
1Aged
2Alzheimers disease
3Amyloid - genetics
4Amyloid - metabolism
5APOE
6Apolipoproteins
7Apolipoproteins E - genetics
8Atherosclerosis
9Biological and medical sciences
10Blood Pressure - physiology
11Calmodulin-Binding Proteins - genetics
12Cerebral Hemorrhage - etiology
13Cerebral Hemorrhage - pathology
14Cerebral small-vessel disease
15Cerebrovascular disease
16Cerebrovascular Disorders - epidemiology
17Cerebrovascular Disorders - etiology
18Cerebrovascular Disorders - genetics
19Cholesterol
20Cognition Disorders - etiology
21Cognition Disorders - psychology
22Cognitive ability
23Cohort Studies
24Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
25Dementia
26Demographic aspects
27Female
28Genes
29Genetic aspects
30Genotype
31Haplotypes
32Health risk assessment
33Humans
34Hypertension
35Hypertension - complications
36Hypertension - epidemiology
37Hypertension - genetics
38LDL-Receptor Related Proteins - genetics
39Magnetic Resonance Imaging
40Male
41Medical sciences
42Membrane Transport Proteins - genetics
43microbleeds
44Middle Aged
45Netherlands - epidemiology
46Neurology
47Neuropsychological Tests
48Pathogenesis
49Polymorphism, Single Nucleotide - genetics
50Population
51RAS
52Receptor, Angiotensin, Type 1 - genetics
53Risk factors
54SORL1
55Studies
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1van Swieten, J C
2Schol-Gelok, S
3Ikram, M A
4Vernooij, M W
5Liu, F
6Isaacs, A
7de Boer, R
8de Koning, I
9Niessen, W J
10Vrooman, H
11Oostra, B A
12van der Lugt, A
13Breteler, M M B
14van Duijn, C M
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8de Koning, I
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abstractBackgroundAsymptomatic 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 MethodsThe 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)).ResultsAll 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).ConclusionThe association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.
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pmid20667857
doi10.1136/jnnp.2009.176362