A study of the association between the ADAM12 and SH3PXD2A (SH3MD1) genes and Alzheimer's disease

Laumet, Geoffroy; Petitprez, Vincent; Sillaire, Adeline Rollin; Ayral, Anne Marie; Hansmannel, Franck; Chapuis, Julien; Hannequin, Didier; Pasquier, Florence; Scarpini, Elio; Galimberti, Daniela; Lendon, Corinne; Campion, Dominique; Amouyel, Philippe; Lambert, Jean‐Charles

doi:10.1016/j.neulet.2009.10.040

Cited by 15 publications

(11 citation statements)

References 8 publications

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“…TKS5 has been shown to be important in determining the invasiveness of cancer cells 13 and has been suggested to mediate the neurotoxic effect of beta-amyloid in Alzheimer disease in association with the matrix metalloproteinase gene ADAM12 . 14 Developmentally, SH3PXD2A is important for neural crest migration; homozygous knockout in mice result in complete cleft in the secondary palate and neonatal death; 15 however, the relation between SH3PXD2A and atrial fibrillation is unclear and as with any rare variant association, replication in a large, independent dataset will ultimately be required.…”

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confidence: 99%

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Christophersen¹,

Rienstra²,

Roselli³

et al. 2017

Nat Genet

276

255

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Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups.3–7 To further define the genetic basis of atrial fibrillation, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with atrial fibrillation and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate new potential targets for drug discovery.8

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mentioning

confidence: 99%

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Christophersen¹,

Rienstra²,

Roselli³

et al. 2017

Nat Genet

276

255

View full text Add to dashboard Cite

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“…Both genes are located on chromosome 10, within a region linked to AD (for SH3PXD2A ) or nearby (for ADAM12 ). Two variants of these genes (rs3740473 for SH3PXD2A and rs11244787 for ADAM12 ) have been associated with increased risk for developing AD, but these findings could not be confirmed in different populations [78]. …”

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: 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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A study of the association between the ADAM12 and SH3PXD2A (SH3MD1) genes and Alzheimer's disease

Cited by 15 publications

References 8 publications

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Genomics of Dementia:APOE- andCYP2D6-Related Pharmacogenetics

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

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