Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage.
| Autor: | Staalsø JM; Department of Neuroscience and Pharmacology, University of Copenhagen; and., Edsen T, Kotinis A, Romner B, Springborg JB, Olsen NV |
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| Jazyk: | angličtina |
| Zdroj: | Journal of neurosurgery [J Neurosurg] 2014 Sep; Vol. 121 (3), pp. 587-92. Date of Electronic Publication: 2014 Jun 27. |
| DOI: | 10.3171/2014.5.JNS131572 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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