title: Polymorphisms in ACVRL1 and endoglin genes are not associated with sporadic and HHT-related brain AVMs in Dutch patients.
abstract: We aimed to replicate the association of the IVS3-35A>G polymorphism in the activin receptor-like kinase (ACVRL) 1 gene and the 207G>A polymorphism in the endoglin (ENG) gene with sporadic brain arteriovenous malformations (BAVM) in Dutch BAVM patients. In addition, we assessed whether these polymorphisms contribute to the risk of BAVM in patients with hereditary haemorrhagic telangiectasia type 1 (HHT1). We genotyped 143 Dutch sporadic BAVM patients and 360 healthy volunteers for four variants in the ACVRL1 gene including IVS3-35A>G and two variants in the ENG gene including 207G>A. Differences in allele and genotype frequencies between sporadic BAVM patients and controls and their combined effect were analysed with a likelihood ratio test. Furthermore, we compared the allele and genotype frequencies between 24 HHT1 patients with a BAVM with those of a relative with HHT1 without a BAVM in a matched pair analysis using Wilcoxon signed rank test. No significant differences in allele frequency were found between sporadic BAVM cases and controls or between HHT1 patients with and without BAVM for any of the polymorphisms or the combination of ACVRL1 and ENG polymorphisms. Meta-analysis of the current and the two previous studies for the ACVRL1 IVS3-35A polymorphism showed a persisting association between the ACVRL1 IVS3-35A polymorphism and risk of sporadic BAVM (odds ratio, 1.86; 95% CI: 1.32-2.61, p<0.001). We did not replicate the previously found association between a polymorphism in ACVRL1 IVS3-35A>G and BAVM in Dutch patients. However, meta-analysis did not rule out a possible effect.
authors: Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
authors: Kim
authors: K
authors: Boshuisen
authors: Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
authors: Manon
authors: M
authors: Brundel
authors: Department of Biomedical Genetics and Complex Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
authors: Carolien G F
authors: CGF
authors: de Kovel
authors: Department of Biomedical Genetics and Complex Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
authors: Tom G
authors: TG
authors: Letteboer
authors: Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
authors: Gabriel J E
authors: GJE
authors: Rinkel
authors: Department of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands.
authors: Cornelis J J
authors: CJJ
authors: Westermann
authors: Department of Anesthesia and Perioperative Care and Department of Epidemiology and Biostatistics, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143-0244, USA.
authors: Helen
authors: H
authors: Kim
authors: Department of Anesthesia and Perioperative Care and Department of Epidemiology and Biostatistics, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143-0244, USA.
authors: Ludmila
authors: L
authors: Pawlikowska
authors: Department of Biomedical Genetics and Complex Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
authors: Bobby P C
authors: BPC
authors: Koeleman
authors: Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
authors: Catharina J M
authors: CJM
authors: Klijn
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D015703:Antigens, CD / Q000235:genetics*; D016022:Case-Control Studies; D000071063:Endoglin; D005260:Female; D005838:Genotype; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II