Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population: A Case-control Study

Jonatan Myrup Staalsø; Morten Nielsen; Troels BS Edsen; Pernille Koefoed; Jacob Bertram Springborg; Finn Borgbjerg Moltke; Henning Laursen; Henning Bay Nielsen; Niels Vidiendal Olsen

doi:10.1097/ana.0b013e318225c979

Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population: A Case-control Study

Jonatan Myrup Staalsø, Morten Nielsen, Troels BS Edsen, Pernille Koefoed, Jacob Bertram Springborg, Finn Borgbjerg Moltke, Henning Laursen, Henning Bay Nielsen, Niels Vidiendal Olsen

Institut for Neurovidenskab

11 Citationer (Scopus)

Abstract

OBJECTIVE: The intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has been associated with rupture of intracranial aneurysms, but the effect of haplotypes within ACE has not been studied. This study investigated whether ACE haplotypes including the I/D polymorphism are associated with aneurysmal subarachnoid hemorrhage. METHODS: The hypothesis was tested with a case-control design in 176 patients with aneurysmal subarachnoid hemorrhage and with 498 hospital controls. Through the pairwise tagging principle, single nucleotide polymorphisms (rs4291 A/T, rs4295 C/G, rs4305 C/T, rs4311 C/T, rs4331 T/C, rs4343 C/T) in the ACE gene were genotyped along with the I/D polymorphism. Haplotypes were estimated using the PHASE software. RESULTS: Fifty-five haplotypes were identified with 3 of these having a frequency above 5%: ACCCCIT (41.6±0.4%), TGTTTDC (32.1±0.5%), and ACCTTDC (9.5±0.2%). No significant difference in distribution of alleles, genotypes, haplotypes, or haplotype pairs between the 2 populations was found. Specifically, we could not reproduce previously reported associations between the ACE I genotype and intracranial aneurysms. When subdivided into groups of aneurysm location, we found a trend toward an association between homozygotes of the ACCCCIT haplotype and middle cerebral artery aneurysms, odds ratio=2.9 (1.0 to 7.6), which however proved insignificant (P=0.22) after correction for multiple testing. CONCLUSION: In this Danish population, ACE haplotypes and the I/D polymorphism did not contribute significantly to the overall risk of intracranial aneurysm rupture. Larger studies are needed to delineate the association between ACE polymorphism and ruptured middle cerebral artery aneurysms.

Originalsprog	Engelsk
Tidsskrift	Journal of Neurosurgical Anesthesiology
Vol/bind	23
Udgave nummer	4
Sider (fra-til)	304-309
Antal sider	6
ISSN	0898-4921
DOI	https://doi.org/10.1097/ana.0b013e318225c979
Status	Udgivet - okt. 2011

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10.1097/ana.0b013e318225c979

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title = "Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population: A Case-control Study",

abstract = "OBJECTIVE: The intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has been associated with rupture of intracranial aneurysms, but the effect of haplotypes within ACE has not been studied. This study investigated whether ACE haplotypes including the I/D polymorphism are associated with aneurysmal subarachnoid hemorrhage. METHODS: The hypothesis was tested with a case-control design in 176 patients with aneurysmal subarachnoid hemorrhage and with 498 hospital controls. Through the pairwise tagging principle, single nucleotide polymorphisms (rs4291 A/T, rs4295 C/G, rs4305 C/T, rs4311 C/T, rs4331 T/C, rs4343 C/T) in the ACE gene were genotyped along with the I/D polymorphism. Haplotypes were estimated using the PHASE software. RESULTS: Fifty-five haplotypes were identified with 3 of these having a frequency above 5%: ACCCCIT (41.6±0.4%), TGTTTDC (32.1±0.5%), and ACCTTDC (9.5±0.2%). No significant difference in distribution of alleles, genotypes, haplotypes, or haplotype pairs between the 2 populations was found. Specifically, we could not reproduce previously reported associations between the ACE I genotype and intracranial aneurysms. When subdivided into groups of aneurysm location, we found a trend toward an association between homozygotes of the ACCCCIT haplotype and middle cerebral artery aneurysms, odds ratio=2.9 (1.0 to 7.6), which however proved insignificant (P=0.22) after correction for multiple testing. CONCLUSION: In this Danish population, ACE haplotypes and the I/D polymorphism did not contribute significantly to the overall risk of intracranial aneurysm rupture. Larger studies are needed to delineate the association between ACE polymorphism and ruptured middle cerebral artery aneurysms.",

author = "Staals{\o}, {Jonatan Myrup} and Morten Nielsen and Edsen, {Troels BS} and Pernille Koefoed and Springborg, {Jacob Bertram} and Moltke, {Finn Borgbjerg} and Henning Laursen and Nielsen, {Henning Bay} and Olsen, {Niels Vidiendal}",

year = "2011",

month = oct,

doi = "10.1097/ana.0b013e318225c979",

language = "English",

volume = "23",

pages = "304--309",

journal = "Journal of Neurosurgical Anesthesiology",

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TY - JOUR

T1 - Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population: A Case-control Study

AU - Staalsø, Jonatan Myrup

AU - Nielsen, Morten

AU - Edsen, Troels BS

AU - Koefoed, Pernille

AU - Springborg, Jacob Bertram

AU - Moltke, Finn Borgbjerg

AU - Laursen, Henning

AU - Nielsen, Henning Bay

AU - Olsen, Niels Vidiendal

PY - 2011/10

Y1 - 2011/10

N2 - OBJECTIVE: The intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has been associated with rupture of intracranial aneurysms, but the effect of haplotypes within ACE has not been studied. This study investigated whether ACE haplotypes including the I/D polymorphism are associated with aneurysmal subarachnoid hemorrhage. METHODS: The hypothesis was tested with a case-control design in 176 patients with aneurysmal subarachnoid hemorrhage and with 498 hospital controls. Through the pairwise tagging principle, single nucleotide polymorphisms (rs4291 A/T, rs4295 C/G, rs4305 C/T, rs4311 C/T, rs4331 T/C, rs4343 C/T) in the ACE gene were genotyped along with the I/D polymorphism. Haplotypes were estimated using the PHASE software. RESULTS: Fifty-five haplotypes were identified with 3 of these having a frequency above 5%: ACCCCIT (41.6±0.4%), TGTTTDC (32.1±0.5%), and ACCTTDC (9.5±0.2%). No significant difference in distribution of alleles, genotypes, haplotypes, or haplotype pairs between the 2 populations was found. Specifically, we could not reproduce previously reported associations between the ACE I genotype and intracranial aneurysms. When subdivided into groups of aneurysm location, we found a trend toward an association between homozygotes of the ACCCCIT haplotype and middle cerebral artery aneurysms, odds ratio=2.9 (1.0 to 7.6), which however proved insignificant (P=0.22) after correction for multiple testing. CONCLUSION: In this Danish population, ACE haplotypes and the I/D polymorphism did not contribute significantly to the overall risk of intracranial aneurysm rupture. Larger studies are needed to delineate the association between ACE polymorphism and ruptured middle cerebral artery aneurysms.

AB - OBJECTIVE: The intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has been associated with rupture of intracranial aneurysms, but the effect of haplotypes within ACE has not been studied. This study investigated whether ACE haplotypes including the I/D polymorphism are associated with aneurysmal subarachnoid hemorrhage. METHODS: The hypothesis was tested with a case-control design in 176 patients with aneurysmal subarachnoid hemorrhage and with 498 hospital controls. Through the pairwise tagging principle, single nucleotide polymorphisms (rs4291 A/T, rs4295 C/G, rs4305 C/T, rs4311 C/T, rs4331 T/C, rs4343 C/T) in the ACE gene were genotyped along with the I/D polymorphism. Haplotypes were estimated using the PHASE software. RESULTS: Fifty-five haplotypes were identified with 3 of these having a frequency above 5%: ACCCCIT (41.6±0.4%), TGTTTDC (32.1±0.5%), and ACCTTDC (9.5±0.2%). No significant difference in distribution of alleles, genotypes, haplotypes, or haplotype pairs between the 2 populations was found. Specifically, we could not reproduce previously reported associations between the ACE I genotype and intracranial aneurysms. When subdivided into groups of aneurysm location, we found a trend toward an association between homozygotes of the ACCCCIT haplotype and middle cerebral artery aneurysms, odds ratio=2.9 (1.0 to 7.6), which however proved insignificant (P=0.22) after correction for multiple testing. CONCLUSION: In this Danish population, ACE haplotypes and the I/D polymorphism did not contribute significantly to the overall risk of intracranial aneurysm rupture. Larger studies are needed to delineate the association between ACE polymorphism and ruptured middle cerebral artery aneurysms.

U2 - 10.1097/ana.0b013e318225c979

DO - 10.1097/ana.0b013e318225c979

M3 - Journal article

C2 - 21709586

SN - 0898-4921

VL - 23

SP - 304

EP - 309

JO - Journal of Neurosurgical Anesthesiology

JF - Journal of Neurosurgical Anesthesiology

IS - 4

ER -

Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population: A Case-control Study

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