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

Jonatan Myrup Staalsø; Troels Edsen; Alexandros Kotinis; Bertil Romner; Jacob Bertram Springborg; Niels Vidiendal Olsen

doi:10.3171/2014.5.jns131572

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

Jonatan Myrup Staalsø, Troels Edsen, Alexandros Kotinis, Bertil Romner, Jacob Bertram Springborg, Niels Vidiendal Olsen

Department of Clinical Medicine

6 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Neurosurgery
Volume	121
Issue number	3
Pages (from-to)	587-92
Number of pages	6
ISSN	0022-3085
DOIs	https://doi.org/10.3171/2014.5.jns131572
Publication status	Published - Sept 2014

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Case-Control Studies
Female
Genotype
Haplotypes
Humans
Introns
Logistic Models
Male
Middle Aged
Nitric Oxide Synthase Type III
Polymorphism, Single Nucleotide
Sex Factors
Subarachnoid Hemorrhage
Tandem Repeat Sequences
Young Adult

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10.3171/2014.5.jns131572

https://thejns.org/downloadpdf/journals/j-neurosurg/121/3/article-p587.pdf

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@article{5e0b3489503f470cae01f8d4b662d308,

title = "Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage",

abstract = "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.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Case-Control Studies, Female, Genotype, Haplotypes, Humans, Introns, Logistic Models, Male, Middle Aged, Nitric Oxide Synthase Type III, Polymorphism, Single Nucleotide, Sex Factors, Subarachnoid Hemorrhage, Tandem Repeat Sequences, Young Adult",

author = "Staals{\o}, {Jonatan Myrup} and Troels Edsen and Alexandros Kotinis and Bertil Romner and Springborg, {Jacob Bertram} and Olsen, {Niels Vidiendal}",

year = "2014",

month = sep,

doi = "10.3171/2014.5.jns131572",

language = "English",

volume = "121",

pages = "587--92",

journal = "Journal of Neurosurgery",

issn = "0022-3085",

publisher = "American Association of Neurological Surgeons",

number = "3",

}

TY - JOUR

T1 - Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage

AU - Staalsø, Jonatan Myrup

AU - Edsen, Troels

AU - Kotinis, Alexandros

AU - Romner, Bertil

AU - Springborg, Jacob Bertram

AU - Olsen, Niels Vidiendal

PY - 2014/9

Y1 - 2014/9

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Case-Control Studies

KW - Female

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Introns

KW - Logistic Models

KW - Male

KW - Middle Aged

KW - Nitric Oxide Synthase Type III

KW - Polymorphism, Single Nucleotide

KW - Sex Factors

KW - Subarachnoid Hemorrhage

KW - Tandem Repeat Sequences

KW - Young Adult

U2 - 10.3171/2014.5.jns131572

DO - 10.3171/2014.5.jns131572

M3 - Journal article

C2 - 24972130

SN - 0022-3085

VL - 121

SP - 587

EP - 592

JO - Journal of Neurosurgery

JF - Journal of Neurosurgery

IS - 3

ER -

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

Abstract

Keywords

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