Association between PDE4D gene and ischemic stroke: recent advancements

Das, Subhra; Roy, Sitara; Munshi, Anjana

doi:10.3109/00207454.2015.1051621

Cited by 13 publications

(9 citation statements)

References 51 publications

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“…One adult patient with acrodysostosis and one child with PDE4D variant have also been described with a deep vein thrombosis [13,23]. Actually, several case-control studies have assigned an association between PDE4D variants and risk of ischemic stroke among different ethnicities [24]. Moreover, PDE4D is associated with inflammation and reduced PDE4D is assumed to predispose individuals to atrial fibrillation, which increases the risk of cardiogenic stroke [25].…”

Section: Discussionmentioning

confidence: 99%

Expanding the phenotypic spectrum of variants in PDE4D/PRKAR1A: from acrodysostosis to acroscyphodysplasia

et al. 2018

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Acrodysostosis (MIM 101800) is a dominantly inherited condition associating (1) skeletal features (short stature, facial dysostosis, and brachydactyly with cone-shaped epiphyses), (2) resistance to hormones and (3) possible intellectual disability. Acroscyphodysplasia (MIM 250215) is characterized by growth retardation, brachydactyly, and knee epiphyses embedded in cup-shaped metaphyses. We and others have identified PDE4D or PRKAR1A variants in acrodysostosis; PDE4D variants have been reported in three cases of acroscyphodysplasia. Our study aimed at reviewing the clinical and molecular findings in a cohort of 27 acrodysostosis and 5 acroscyphodysplasia cases. Among the acrodysostosis cases, we identified 9 heterozygous de novo PRKAR1A variants and 11 heterozygous PDE4D variants. The 7 patients without variants presented with symptoms of acrodysostosis (brachydactyly and cone-shaped epiphyses), but none had the characteristic facial dysostosis. In the acroscyphodysplasia cases, we identified 2 PDE4D variants. For 2 of the 3 negative cases, medical records revealed early severe infection, which has been described in some reports of acroscyphodysplasia. Subdividing our series of acrodysostosis based on the disease-causing gene, we confirmed genotype-phenotype correlations. Hormone resistance was consistently observed in patients carrying PRKAR1A variants, whereas no hormone resistance was observed in 9 patients with PDE4D variants. All patients with PDE4D variants shared characteristic facial features (midface hypoplasia with nasal hypoplasia) and some degree of intellectual disability. Our findings of PDE4D variants in two cases of acroscyphodysplasia support that PDE4D may be responsible for this severe skeletal dysplasia. We eventually emphasize the importance of some specific assessments in the long-term follow up, including cardiovascular and thromboembolic risk factors.

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Section: Discussionmentioning

confidence: 99%

Expanding the phenotypic spectrum of variants in PDE4D/PRKAR1A: from acrodysostosis to acroscyphodysplasia

et al. 2018

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“…There has been much interest in the PDE4 family because of its potential as a therapeutic target [20], that mutations in PDE4D are associated with acrodysostosis [21] and that PDE4 gene linkages are associated with tumour development including prostate cancer (PDE4D) [22], psychiatric illness (PDE4B) [23] and stroke (PDE4D) [24]. Furthermore, PDE4 members play critical cellular roles in underpinning cAMP signalling compartmentalization within cells [13].…”

Section: Cyclic Amp Phosphodiesterasesmentioning

confidence: 99%

“…The PDE4D7 promoter has been identified with initial studies identifying multiple CREB binding sites (CRE loci), suggesting that the cAMP/PKA signalling pathway may regulate PDE4D7 transcriptional expression [65]. Otherwise, little more is known, save that susceptibility markers for ischaemic stroke map to the region of Chr5q12 where PDE4D7, and the overlapping androgen-sensitive PART1 exons, locate [24,[65][66][67][68].…”

Section: The Intracellular Function and Regulation Of Pde4d7mentioning

confidence: 99%

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

et al. 2019

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Increased PSA-based screening for prostate cancer has resulted in a growing number of diagnosed cases. However, around half of these are ‘indolent’, neither metastasizing nor leading to disease specific death. Treating non-progressing tumours with invasive therapies is currently regarded as unnecessary over-treatment with patients being considered for conservative regimens, such as active surveillance (AS). However, this raises both compliance and protocol issues. Great clinical benefit could accrue from a biomarker able to predict long-term patient outcome accurately at the time of biopsy and initial diagnosis. Here we delineate the translation of a laboratory discovery through to the precision development of a clinically validated, novel prognostic biomarker assay (InformMDx™). This centres on determining transcript levels for phosphodiesterase-4D7 (PDE4D7), an enzyme that breaks down cyclic AMP, a signalling molecule intimately connected with proliferation and androgen receptor function. Quantifiable detection of PDE4D7 mRNA transcripts informs on the longitudinal outcome of post-surgical disease progression. The risk of post-surgical progression increases steeply for patients with very low ‘PDE4D7 scores’, while risk decreases markedly for those patients with very high ‘PDE4D7 scores’. Combining clinical risk variables, such as the Gleason or CAPRA (Cancer of the Prostate Risk Assessment) score, with the ‘PDE4D7 score’ further enhances the prognostic power of this personalized, precision assessment. Thus the ‘PDE4D7 score’ has the potential to define, more effectively, appropriate medical intervention/AS strategies for individual prostate cancer patients.

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“…first identified the association of SNP83 in the PDE4D gene with carotid stroke in an Icelandic population 11 . Since then, many studies have found such association in various populations 12 . Woo et al .…”

mentioning

confidence: 94%

Phosphodiesterase 4D polymorphisms associate with the short-term outcome in ischemic stroke

Song

Wang

et al. 2017

Sci Rep

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It has been demonstrated that phosphodiesterase 4D (PDE4D) genetic polymorphism is associated with ischemic stroke. However, the association between PDE4D gene and prognosis after ischemic stroke remains unknown. We consecutively enrolled ischemic stroke patients admitted to Beijing Tiantan Hospital from October 2009 to December 2013. Clinical, laboratory and imaging data upon admission were collected. All patients were followed up 3 months after stroke onset. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the associations of genetic polymorphisms with 3-month outcome after ischemic stroke and different subtypes, under various genetic models. A total of 1447 patients were enrolled, and 3-month follow-up data were obtained from 1388 (95.92%). Multivariate regression analysis showed that SNP87 of PDE4D gene was associated with increased risk of unfavorable outcome after total ischemic stroke (OR = 1.47, 95%CI 1.12–1.93), as well as stroke due to large-artery atherosclerosis (OR = 1.49, 95%CI 1.04–2.11) and small-artery occlusion (OR = 1.76, 95%CI 1.05–2.96) under a recessive model. No association between SNP83 genotype and poor outcome was found. Overall, this study demonstrated that the TT genotype of SNP87 in PDE4D was associated with increased risk of poor outcome after total ischemic stroke, large-artery atherosclerosis and small-artery occlusion, in a Chinese population.

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Association between PDE4D gene and ischemic stroke: recent advancements

Cited by 13 publications

References 51 publications

Expanding the phenotypic spectrum of variants in PDE4D/PRKAR1A: from acrodysostosis to acroscyphodysplasia

Expanding the phenotypic spectrum of variants in PDE4D/PRKAR1A: from acrodysostosis to acroscyphodysplasia

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

Phosphodiesterase 4D polymorphisms associate with the short-term outcome in ischemic stroke

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