Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population

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

doi:10.1097/ana.0b013e318225c979

Cited by 15 publications

(13 citation statements)

References 31 publications

(37 reference statements)

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“…Certain previous studies investigated the influence of ACE I/D gene polymorphisms on IA susceptibility (17)(18)(19)(20)(21)(22)(23); however, the results of these studies remain inconsistent. As a single study might not be powered to demonstrate the overall effects, Association between angiotensin-converting enzyme insertion/deletion polymorphisms and intracranial aneurysm susceptibility: A meta-analysis a meta-analysis using currently available data was performed in the present study to detect the potential association of ACE I/D gene polymorphisms on IA risk.…”

Section: Introductionmentioning

confidence: 56%

“…Subsequently, various studies with conflicting opinions have been reported (18,19,23). A previous meta-analysis failed to detect an association between the ACE I/D polymorphism and IA susceptibility in the dominant (OR=1.23, 95% CI=0.82-1.85; P OR =0.31) or the recessive (OR=1.58, 95% CI=0.98-2.57; P OR =0.06) models (11).…”

Section: Codominant Model -------------------------------------------mentioning

confidence: 99%

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Association between angiotensin-converting enzyme insertion/deletion polymorphisms and intracranial aneurysm susceptibility: A meta-analysis

et al. 2017

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Abstract.Various studies have evaluated the association between polymorphisms of angiotensin-converting enzyme (ACE) and intracranial aneurysm (IA) risk; however, the results remain inconsistent. The PubMed, Embase, and Wanfang Data databases were systematically searched until January 6th 2016. Case-control studies investigating the association between the ACE polymorphism and IA risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with the fixed or random-effects model assuming allele, homozygote comparison of codominant, heterozygote comparison of codominant, dominant, and recessive models. Seven studies including 1,074 cases and 1,500 controls were included in the current meta-analysis. The results of the analysis indicated that the ACE polymorphism significantly increased IA risk in the allele, homozygote comparison of codominant and dominant models. According to the further stratified analysis by ethnicity, source of control and sample sizes, a significant association was identified between the ACE variant and IA risk in Asian individuals, hospital-based, or large (>300) subgroups in all of the genetic models, not including the recessive model. Furthermore, no significantly increased risk was indicated in Caucasian individuals, population-based, or small (<300) subgroups in the heterozygote comparison of codominant, dominant and recessive models. The available evidence indicates that the ACE polymorphism is associated with an increased risk of IA, particularly in Asian individuals. However, other factors may impact this association. Further large, well-designed multicenter studies are required to validate the findings from the present study.

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Section: Introductionmentioning

confidence: 56%

Section: Codominant Model -------------------------------------------mentioning

confidence: 99%

Association between angiotensin-converting enzyme insertion/deletion polymorphisms and intracranial aneurysm susceptibility: A meta-analysis

et al. 2017

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“…A subpopulation of the participants were part of another genetic association study concerning the effects of the ACE I/D polymorphism, which found no association with SAH. 30 …”

Section: Participantsmentioning

confidence: 99%

Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage

Staalsø

Edsen²,

Kotinis³

et al. 2014

JNS

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Object. The nitric oxide system has been linked to the pathogenesis of aneurysmal subarachnoid hemorrhage (SAH). The authors performed a case-control study to investigate the association between SAH and common genetic variants within the endothelial nitric oxide synthase gene (NOS3).Methods. Three hundred thirty-three Caucasian SAH patients and 498 controls were genotyped for the -922A > G (rs 1800779), -786T > C (rs2070744), and 894G > T (rs1799983) single nucleotide polymorphisms and the intron-4 27-bp variable number of tandem repeats polymorphism (27-bp-VNTR).Results. The b/b (5 repeats) genotype of the 27-bp-VNTR was overrepresented in cases (77%) versus controls (69%) (p = 0.02). In male patients the b/b genotype was found in 85% compared with 67% in male controls, whereas in women, the frequencies were 73% and 72%, respectively. This corresponds to an odds ratio of 2.8 (95% CI 1.5-5.6, p = 0.0005) for SAH in men with the b/b genotype versus men with a/b or a/a. In women, no such association was found (OR 1.1, 95% CI 0.7-1.6, p = 0.76). Stepwise logistic regression including arterial hypertension, smoking, sex, and age with interactions yielded similar effect estimates of the 27-bp-VNTR. Haplotype analysis revealed that no single haplotype containing the b-allele was responsible for the observed genotype effect.Conclusions. The authors' results suggest that the NOS3 27-bp-VNTR b/b genotype independent of other risk factors act in concert with male sex to substantially increase risk of SAH. This effect is not mediated by any single NOS3 haplotype.

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“…[25][26][27][28][29][30][31][32][33] Finally, a total of six studies were included in our meta-analysis, which included 744 ICH cases and 1411 controls. [19][20][21][22][23][24] Study characteristics are summarized in Table 1. Of those, one study included population-based case-control studies, and five studies included hospitalbased case-control studies.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Through the step of screening the title and abstracts, 83 articles were excluded, leaving 15 articles for full publication review. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Of these, nine were excluded. [25][26][27][28][29][30][31][32][33] Finally, a total of six studies were included in our meta-analysis, which included 744 ICH cases and 1411 controls.…”

Section: Study Characteristicsmentioning

confidence: 99%

Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: A meta-analysis of epidemiologic studies

Huang¹,

Li²,

Lan³

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Studies investigating the association between the intron 16 insertion/deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) gene and risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratios (OR) and 95% confidence limits (CLs) were calculated in fixed-or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 744 ICH cases and 1411 controls. The combined results based on all studies showed that ICH cases had a significantly lower frequency of ID genotype (OR (codominant model) = 0.43, 95% CL = 0.22, 0.84, p = 0.01). In the subgroup analysis by race, we found that ICH cases had a significantly lower frequency of II genotype in Asians (OR (recessive model) = 0.50, 95% CL = 0.38, 0.66, p < 0.001; OR (codominant model) = 0.25, 95% CL = 0.09, 0.71, p = 0.009). In conclusion, our meta-analysis suggests that ACE I/D polymorphisms are associated with ICH, especially in Asians.

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Common Variants of the ACE Gene and Aneurysmal Subarachnoid Hemorrhage in a Danish Population

Abstract: 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.

Cited by 15 publications

References 31 publications

Association between angiotensin-converting enzyme insertion/deletion polymorphisms and intracranial aneurysm susceptibility: A meta-analysis

Association between angiotensin-converting enzyme insertion/deletion polymorphisms and intracranial aneurysm susceptibility: A meta-analysis

Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage

Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: A meta-analysis of epidemiologic studies

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