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

doi:10.1136/jnnp.2009.176362

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Pages (from-to)	41-4
Number of pages	4
Journal	Journal of Neurology Neurosurgery and Psychiatry
Volume	82
Issue number	1
DOIs	https://doi.org/10.1136/jnnp.2009.176362
Publication status	Published - Jan 2011
Externally published	Yes

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

Access to Document

10.1136/jnnp.2009.176362

Cite this

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. (2011). Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population. Journal of Neurology Neurosurgery and Psychiatry, 82(1), 41-4. https://doi.org/10.1136/jnnp.2009.176362

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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.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.",

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",

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

year = "2011",

month = jan,

doi = "10.1136/jnnp.2009.176362",

language = "English",

volume = "82",

pages = "41--4",

journal = "Journal of Neurology Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group",

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Schuur, M, van Swieten, JC, Schol-Gelok, S, Ikram, MA, Vernooij, MW, Liu, F, Isaacs, A, de Boer, R, de Koning, I, Niessen, WJ, Vrooman, H, Oostra, BA, van der Lugt, A, Breteler, MMB & van Duijn, CM 2011, 'Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population', Journal of Neurology Neurosurgery and Psychiatry, vol. 82, no. 1, pp. 41-4. https://doi.org/10.1136/jnnp.2009.176362

TY - JOUR

T1 - Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population

AU - Schuur, M

AU - van Swieten, J C

AU - Schol-Gelok, S

AU - Ikram, M A

AU - Vernooij, M W

AU - Liu, F

AU - Isaacs, A

AU - de Boer, R

AU - de Koning, I

AU - Niessen, W J

AU - Vrooman, H

AU - Oostra, B A

AU - van der Lugt, A

AU - Breteler, M M B

AU - van Duijn, C M

PY - 2011/1

Y1 - 2011/1

N2 - 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.

AB - 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.

KW - Aged

KW - Amyloid/genetics

KW - Apolipoproteins E/genetics

KW - Blood Pressure/physiology

KW - Calmodulin-Binding Proteins/genetics

KW - Cerebral Hemorrhage/etiology

KW - Cerebrovascular Disorders/epidemiology

KW - Cognition Disorders/etiology

KW - Cohort Studies

KW - Female

KW - Genotype

KW - Humans

KW - Hypertension/complications

KW - LDL-Receptor Related Proteins/genetics

KW - Magnetic Resonance Imaging

KW - Male

KW - Membrane Transport Proteins/genetics

KW - Middle Aged

KW - Netherlands/epidemiology

KW - Neuropsychological Tests

KW - Polymorphism, Single Nucleotide/genetics

KW - Receptor, Angiotensin, Type 1/genetics

U2 - 10.1136/jnnp.2009.176362

DO - 10.1136/jnnp.2009.176362

M3 - Article

C2 - 20667857

SN - 0022-3050

VL - 82

SP - 41

EP - 44

JO - Journal of Neurology Neurosurgery and Psychiatry

JF - Journal of Neurology Neurosurgery and Psychiatry

IS - 1

ER -