Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

P H C Kremer; B P C Koeleman; G Je Rinkel; F P Diekstra; L H van den Berg; J H Veldink; C J M Klijn

doi:10.1136/jnnp-2014-310094

Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

P H C Kremer, B P C Koeleman, G Je Rinkel, F P Diekstra, L H van den Berg, J H Veldink, C J M Klijn

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results. Methods We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by Χ<sup>2</sup> testing in Plink V.1.07. Meta-analysis was performed in RevMan V.5.3. Results In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1β, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005). Conclusions The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1β, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis.

Original language	English
Pages (from-to)	693-6
Number of pages	4
Journal	Journal of Neurology, Neurosurgery and Psychiatry
Volume	87
Issue number	7
DOIs	https://doi.org/10.1136/jnnp-2014-310094
Publication status	Published - Jul 2016

Keywords

Adult
Angiopoietin-Like Protein 4
Angiopoietins/genetics
Case-Control Studies
Female
Gene Frequency/genetics
Genetic Loci/genetics
Genetic Predisposition to Disease/genetics
Genome-Wide Association Study
Genotype
Humans
Interleukin-1beta/genetics
Intracranial Arteriovenous Malformations/genetics
Male
Matrix Metalloproteinase 3/genetics
Middle Aged
Polymorphism, Single Nucleotide/genetics
Receptors, G-Protein-Coupled/genetics
Reproducibility of Results
Vascular Endothelial Growth Factor A/genetics

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10.1136/jnnp-2014-310094

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@article{2dc36f5e31014d669f4671bb45760b0b,

title = "Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis",

abstract = "Background Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results. Methods We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by Χ2 testing in Plink V.1.07. Meta-analysis was performed in RevMan V.5.3. Results In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1β, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005). Conclusions The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1β, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis.",

keywords = "Adult, Angiopoietin-Like Protein 4, Angiopoietins/genetics, Case-Control Studies, Female, Gene Frequency/genetics, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Genotype, Humans, Interleukin-1beta/genetics, Intracranial Arteriovenous Malformations/genetics, Male, Matrix Metalloproteinase 3/genetics, Middle Aged, Polymorphism, Single Nucleotide/genetics, Receptors, G-Protein-Coupled/genetics, Reproducibility of Results, Vascular Endothelial Growth Factor A/genetics",

author = "Kremer, {P H C} and Koeleman, {B P C} and Rinkel, {G Je} and Diekstra, {F P} and {van den Berg}, {L H} and Veldink, {J H} and Klijn, {C J M}",

note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/",

year = "2016",

month = jul,

doi = "10.1136/jnnp-2014-310094",

language = "English",

volume = "87",

pages = "693--6",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group",

number = "7",

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TY - JOUR

T1 - Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

AU - Kremer, P H C

AU - Koeleman, B P C

AU - Rinkel, G Je

AU - Diekstra, F P

AU - van den Berg, L H

AU - Veldink, J H

AU - Klijn, C J M

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PY - 2016/7

Y1 - 2016/7

N2 - Background Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results. Methods We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by Χ2 testing in Plink V.1.07. Meta-analysis was performed in RevMan V.5.3. Results In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1β, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005). Conclusions The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1β, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis.

AB - Background Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results. Methods We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by Χ2 testing in Plink V.1.07. Meta-analysis was performed in RevMan V.5.3. Results In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1β, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005). Conclusions The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1β, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis.

KW - Adult

KW - Angiopoietin-Like Protein 4

KW - Angiopoietins/genetics

KW - Case-Control Studies

KW - Female

KW - Gene Frequency/genetics

KW - Genetic Loci/genetics

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Interleukin-1beta/genetics

KW - Intracranial Arteriovenous Malformations/genetics

KW - Male

KW - Matrix Metalloproteinase 3/genetics

KW - Middle Aged

KW - Polymorphism, Single Nucleotide/genetics

KW - Receptors, G-Protein-Coupled/genetics

KW - Reproducibility of Results

KW - Vascular Endothelial Growth Factor A/genetics

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U2 - 10.1136/jnnp-2014-310094

DO - 10.1136/jnnp-2014-310094

M3 - Article

C2 - 26272027

AN - SCOPUS:84940194600

SN - 0022-3050

VL - 87

SP - 693

EP - 696

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 7

ER -

Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

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