Lack of association between NOS3 polymorphism and Italian sporadic and familial Alzheimer's disease

Tedde, Andrea; Nacmias, Benedetta; Cellini, Elena; Bagnoli, Silvia; Sorbi, Sandro

doi:10.1007/pl00007839

Cited by 20 publications

(9 citation statements)

References 5 publications

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“…Genetic association studies between NOS3 and AD have lead to mixed results. An over-representation of the Glu/Glu genotype for the polymorphic variant at amino acid position 298 of NOS3 (Glu298Asp) was observed among late-onset AD cases in UK and Italian populations (12,13), while studies in two other Italian samples and one UK sample, as well as in Japanese, US Caucasian, Swedish, Hungarian, Polish and Hispanic samples, did not find significant association (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). It is unclear whether the discrepant results among these studies is due to limited sample size, suboptimal matching between cases and controls, or varying effects of the Glu298Asp polymorphism across diverse populations.…”

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confidence: 99%

Genetic association between endothelial nitric oxide synthase and Alzheimer disease

Akomolafe

Lunetta²,

Erlich³

et al. 2006

Clinical Genetics

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Evidence suggests that vascular and inflammatory factors may be important in the etiology of Alzheimer disease (AD). The Glu/Glu genotype at the Glu298Asp variant of the endothelial nitric oxide synthase (NOS3) gene has been tested for association with AD in several Caucasian and Asian populations, with conflicting results. We tested the Glu298Asp variant for association in African American and Caucasian AD patients, unaffected siblings, and unrelated controls from the MIRAGE Study. To explore whether the inconsistent results in previous studies might be due to linkage disequilibrium with a polymorphism or haplotype not previously tested, we genotyped 10 additional NOS3 single nucleotide polymorphisms (SNPs) spanning 25.3 kb. Finally, we compiled results of previous studies of Glu298Asp using meta-analysis, to determine whether the aggregate studies support an association between Glu298Asp and AD. We found that the Glu298 allele was associated with higher risk of AD in the MIRAGE African American (p = 0.002) but not Caucasian (p = 0.9) groups. None of the additional SNPs were associated with AD in the Caucasians, whereas two showed evidence for association in the African Americans. The meta-analysis showed a small effect of the Glu298Asp GG genotype on AD risk across all studies (summary odds ratio = 1.15, 95% confidence interval: 0.97-1.35) and significant heterogeneity of this association among studies (p = 0.02).

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confidence: 99%

Genetic association between endothelial nitric oxide synthase and Alzheimer disease

Akomolafe

Lunetta²,

Erlich³

et al. 2006

Clinical Genetics

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“…Dahiyat et al (1999) first found a significant association of LOAD and homozygosity for the Glu allele and the Glu/ Glu genotype of NOS3 Glu298Asp polymorphism. The finding was confirmed by subsequent studies (Guidi et al 2005;Ntais and Polycarpou 2005;Akomolafe et al 2006), but others have failed to find a significant association (Singleton et al 2001;Kálmán et al 2003;Monastero et al 2003;Tedde et al 2002;Sánchez-Guerra et al 2001;Kunugi et al 2000;Wang et al 2004).…”

Section: Introductionmentioning

confidence: 49%

“…The Glu allele frequencies of the Glu298Asp polymorphism in the Chinese population in our study (88.0%), in Japanese (93.3%), in African American (84.0%), and Caucasian American and European populations (62-75%) implied the differences in genetic background (Guidi et al 2005;Ntais and Polycarpou 2005;Akomolafe et al 2006;Kálmán et al 2003;Monastero et al 2003;Tedde et al 2002;Sánchez-Guerra et al 2001;Kunugi et al 2000).…”

Section: Discussionmentioning

confidence: 66%

Association Between Alzheimer’s Disease and the NOS3 gene Glu298Asp Polymorphism in Chinese

et al. 2008

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The oxidative stress caused by nitric oxide (NO) in the brain has been proposed as a pathogenic mechanism in Alzheimer's disease. Endothelial NO synthase (ecNOS) produces the majority of circulating NO. The biological functional and genetic association studies suggested that the Glu298Asp polymorphism of the ecNOS gene (NOS3) may be a genetic risk factor for late-onset Alzheimer's disease (LOAD). To investigate an association between the NOS31 Glu298Asp polymorphism and sporadic LOAD in Chinese, we examined 338 LOAD patients and 378 healthy controls. The associations of the Glu/Glu genotype and Glu allele with LOAD (chi2 = 9.12, df = 1, P = 0.003 by genotype; chi2 = 8.37, df = 1, P = 0.038 by allele) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon 4) status, increased LOAD risks associated with the Glu/Glu genotype and Glu allele only in the APOE epsilon 4 noncarriers (chi2 = 6.28, df = 1, P = 0.012 by genotype; chi2 = 5.62, df = 1, P = 0.018 by allele) were seen. These results suggest that the NOS3 gene Glu298Asp polymorphism might be a risk factor for LOAD and dependent on APOE epsilon 4 status in Chinese.

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“…Another possibility is that the variation simply could be associated with another unknown pathological locus [145]. Subsequent studies in different populations failed to replicate this original finding [94,[147][148][149][150][151][152][153][154], so that, even if not wholly excluded, this genetic polymorphism is unlikely to be a significant susceptibility marker for AD [54].…”

Section: Endothelial Nitric Oxide Synthasementioning

confidence: 86%

The Role of Vascular Factors in Late-Onset Sporadic Alzheimers Disease. Genetic and Molecular Aspects

Rocchi¹,

Orsucci²,

Tognoni

et al. 2009

CAR

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Alzheimer's disease (AD) is a late-onset progressive neurodegenerative disorder which results in the irreversible loss of cortical neurons, particularly in the associative neocortex and hippocampus. AD is the most common form of dementia in the elderly. Apart from the neuronal loss, the pathological hallmarks are extracellular senile plaques, containing the peptide beta-amyloid (Abeta), and neurofibrillary tangles. The Abeta cascade hypothesis remains the main pathogenetic model, as suggested by familiar AD, mainly associated to mutation in amyloid precursor protein and presenilin genes. The remaining 95% of AD patients are mostly sporadic late-onset cases, with a complex aetiology due to interactions between environmental conditions and genetic features of the individual. A relationship between genetic and acquired vascular factors and AD has been hypothesized. Many vascular risk factors for AD, such as atherosclerosis, stroke and cardiac disease in the aging individual, could result in cerebrovascular dysfunction and trigger AD pathology. A major vascular susceptibility factor gene is the apolipoprotein E gene, found to be associated with sporadic late-onset AD cases. Another interesting vascular susceptibility gene is angiotensin converting enzyme. Other possible genes include VLDL-R, LRP, NOS3, CST3, OLR1, MTHFR, PON1 and VEGF, but many of the related studies have shown conflicting results. In this paper, we review the role of molecular vascular abnormalities and of the "vascular risk" genes supposed to be involved in the pathogenesis of AD, in an attempt to provide a comprehensive picture of what is known about the mechanisms underlying the role of vascular factors in late-onset sporadic AD.

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Lack of association between NOS3 polymorphism and Italian sporadic and familial Alzheimer's disease

Cited by 20 publications

References 5 publications

Genetic association between endothelial nitric oxide synthase and Alzheimer disease

Genetic association between endothelial nitric oxide synthase and Alzheimer disease

Association Between Alzheimer’s Disease and the NOS3 gene Glu298Asp Polymorphism in Chinese

The Role of Vascular Factors in Late-Onset Sporadic Alzheimers Disease. Genetic and Molecular Aspects

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