−1154G/A and −2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to β-amyloid (1–42) and total tau protein

Smach, Mohamed Ali; Charfeddine, Bassem; Othman, Leila Ben; Lammouchi, Turkia; Ltaief, Afef; Nafati, Souhir; Dridi, Hedi; Bennamou, Soufien; Limem, Khalifa

doi:10.1016/j.neulet.2010.01.073

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…In a Tunisian population, Smach et al [64] found that the distribution of genotype and allele frequencies of the VEGF (−2578C/A) and (−1154G/A) polymorphisms did not differ significantly between AD and control groups. In the subgroup of APOE-4 carriers, the −2578A was observed to be significantly higher in the AD patients than in the control individuals.…”

Section: Structural Genomics Of Alzheimer's Diseasementioning

confidence: 99%

Genomics of Dementia:APOE- andCYP2D6-Related Pharmacogenetics

Cacabelos

Martínez

Fernández‐Novoa

et al. 2012

International Journal of Alzheimer's Disease

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Dementia is a major problem of health in developed societies. Alzheimer's disease (AD), vascular dementia, and mixed dementia account for over 90% of the most prevalent forms of dementia. Both genetic and environmental factors are determinant for the phenotypic expression of dementia. AD is a complex disorder in which many different gene clusters may be involved. Most genes screened to date belong to different proteomic and metabolomic pathways potentially affecting AD pathogenesis. The ε4 variant of the APOE gene seems to be a major risk factor for both degenerative and vascular dementia. Metabolic factors, cerebrovascular disorders, and epigenetic phenomena also contribute to neurodegeneration. Five categories of genes are mainly involved in pharmacogenomics: genes associated with disease pathogenesis, genes associated with the mechanism of action of a particular drug, genes associated with phase I and phase II metabolic reactions, genes associated with transporters, and pleiotropic genes and/or genes associated with concomitant pathologies. The APOE and CYP2D6 genes have been extensively studied in AD. The therapeutic response to conventional drugs in patients with AD is genotype specific, with CYP2D6-PMs, CYP2D6-UMs, and APOE-4/4 carriers acting as the worst responders. APOE and CYP2D6 may cooperate, as pleiotropic genes, in the metabolism of drugs and hepatic function. The introduction of pharmacogenetic procedures into AD pharmacological treatment may help to optimize therapeutics.

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Section: Structural Genomics Of Alzheimer's Diseasementioning

confidence: 99%

Genomics of Dementia:APOE- andCYP2D6-Related Pharmacogenetics

Cacabelos

Martínez

Fernández‐Novoa

et al. 2012

International Journal of Alzheimer's Disease

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“…In a Tunisian population, Smach et al [59] found that the distribution of genotype and allele frequencies of the VEGF (-2578C/A) and (-1154G/A) polymorphisms did not differ significantly between AD and control groups. In the subgroup of APOE-4 carriers, the -2578A was observed to be significantly higher in the AD patients than in the control individuals.…”

Section: Genomics Of Dementiamentioning

confidence: 99%

Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants

et al. 2010

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About 80% of functional genes in the human genome are expressed in the brain and over 1,200 different genes have been associated with the pathogenesis of CNS disorders and dementia. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variations in specific candidate genes and the positive and adverse effects of drug treatment. Approximately, 18% of neuroleptics are substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. 10-20% of Western populations are defective in genes of the CYP superfamily; and the pharmacogenomic response of psychotropic drugs also depends on genetic variants associated with dementia. Prospective studies with anti-dementia drugs or with multifactorial strategies have revealed that the therapeutic response to conventional drugs in Alzheimer’s disease is genotype-specific. The disease-modifying effects (cognitive performance, biomarker modification) of therapeutic intervention are APOE-dependent, with APOE-4 carriers acting as the worst responders (APOE-3/3 > APOE-3/4 > APOE-4/4). APOE-CYP2D6 interactions also influence the therapeutic outcome in patients with dementia.

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“…In this case-control study, we investigated whether the −75 G/A polymorphism of the apoA1 gene may be responsible for susceptibility to AD in a sample of patients that was already genotyped for apoE, bleomycin hydrolase, and vascular endothelial growth factor (VEGF) [18,19], and to assess its relationship with the severity of the disease as estimated by the Mini-Mental State Examination (MMSE) score.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in apoA1 Influences High-Density Lipoprotein Cholesterol Levels but Is Not a Major Risk Factor of Alzheimer’s Disease

Smach

Edziri

Charfeddine

et al. 2012

Dement Geriatr Cogn Disord Extra

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Background: Apolipoprotein A1 (apoA1) is the major apolipoprotein constituent of the high-density lipoprotein (HDL) and is involved in reverse cholesterol transport. Variation in the apoA1 gene might influence the function of the protein and, thus, brain cholesterol metabolism, leading to an increased risk for Alzheimer’s disease (AD). Aim: In the current report, we investigated the role of the functional apoA1 polymorphism (–75 G/A) as a genetic risk factor for AD in a Tunisian population. Methods: 173 AD patients and 150 healthy controls were studied. Results: No association was found between this genetic variation in apoA1 gene and the risk of AD. The presence of the (–75 G/A) A allele appeared, however, to be associated with lower levels of cerebrospinal fluid Aβ42 and HDL cholesterol levels in sera. Conclusion: Our data support the observation that apoA1 polymorphism influences cholesterol metabolism and Aβ42 deposition in the brain.

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−1154G/A and −2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to β-amyloid (1–42) and total tau protein

Cited by 12 publications

References 26 publications

Genomics of Dementia:APOE- andCYP2D6-Related Pharmacogenetics

Genomics of Dementia:APOE- andCYP2D6-Related Pharmacogenetics

Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants

Polymorphism in apoA1 Influences High-Density Lipoprotein Cholesterol Levels but Is Not a Major Risk Factor of Alzheimer’s Disease

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