Influence of BDNF polymorphisms on Wilson’s disease susceptibility and clinical course

Mirowska‐Guzel, Dagmara; Litwin, Tomasz; Gromadzka, Grażyna; Członkowski, Andrzej; Członkowska, Anna

doi:10.1007/s11011-013-9399-x

Cited by 8 publications

(8 citation statements)

References 34 publications

(42 reference statements)

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“…To ensure that the age of onset of WD is not vastly different between individuals carrying ԑ4 allele and those who are not, we checked the age distribution and mean age of both the groups, suggesting that presence of ԑ4 allele is not affecting survival of the patients (mean age, 13.07 ± 5.57 vs. mean age, 12.45 ± 5.53; P‐ value = 0.61). Similar to our finding, other studies on WD reported that variants of DMT1 and BDNF are associated with the disease (Przybylkowski, Gromadzka, & Czlonkowska, ; Mirowska et al., ), although no plausible explanation could be provided behind the association. Expressional variability, incomplete penetrance, environmental influences or epigenetic modifications are common features for a complex disease; however, recent studies imparted knowledge about such complexity to occur even in case of a monogenic disease.…”

Section: Discussionsupporting

confidence: 89%

Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease

Roy

Ganguly²,

Pal

et al. 2017

Annals of Human Genetics

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Wilson disease (WD) is an autosomal-recessive disorder caused by mutations in the ATP7B gene leading to abnormal copper deposition in liver and brain. WD manifests diverse neurological and hepatic phenotypes and different age of onset, even among the siblings, with same mutational background suggesting complex nature of the disease and involvement of other candidate genes. In that context, Apolipoprotein E (APOE) and Prion Protein (PRNP) have been proposed to be potential candidates for modifying the WD phenotype and age of onset. This study aims to identify the contribution of APOE and PRNP polymorphisms on the variable phenotypic expression of Indian WD patients. A total of 171 WD patients and 291 controls from Indian population were included in this study. Two APOE cSNPs (rs429358 and rs7412) resulting in three isoforms and M129V (rs1799990) polymorphism of PRNP were examined for their association with WD and its clinical phenotypes. The APOE ԑ4 allele was found to be significantly overrepresented in WD patients compared to controls. However, the frequency of the APOE ԑ3 allele and ԑ3/ԑ3 genotype was significantly higher in WD patients without cognitive behavior impairment compared to the ones with the impairment. On the contrary, the PRNP allele representing Val129 was found to be present in higher proportion in WD patients with cognitive behavioral decline. Our data suggest that the APOE ԑ4 allele could act as a potential risk for the pathogenesis of WD. Also, APOE and PRNP might contribute toward the cognitive behavioral decline in a section of WD patients.

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Section: Discussionsupporting

confidence: 89%

Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease

Roy

Ganguly²,

Pal

et al. 2017

Annals of Human Genetics

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“…82 Patients with WD more frequently harbored BDNF polymorphisms [Val/Val (−196 G/G) and −270 C/T] than healthy controls and asymptomatic WD patients. 83 However, no association was identified between any BDNF polymorphism and disease presentation (hepatic vs. neurological) or age of onset of WD.…”

Section: Potential Modifier Genesmentioning

confidence: 98%

“…155 Furthermore, certain SNPs in BDNF are more frequent in symptomatic WD patients versus healthy controls and asymptomatic WD patients. 83 In humans, meditation can increase BDNF levels, 156 alters histone modifications, and downregulates proinflammatory genes. 151 …”

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Kieffer

Medici

2017

Liver Research

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Environmental factors, including diet, exercise, stress, and toxins, profoundly impact disease phenotypes. This review examines how Wilson disease (WD), an autosomal recessive genetic disorder, is influenced by genetic and environmental inputs. WD is caused by mutations in the copper-transporter gene ATP7B, leading to the accumulation of copper in the liver and brain, resulting in hepatic, neurological, and psychiatric symptoms. These symptoms range in severity and can first appear anytime between early childhood and old age. Over 300 disease-causing mutations in ATP7B have been identified, but attempts to link genotype to the phenotypic presentation have yielded little insight, prompting investigators to identify alternative mechanisms, such as epigenetics, to explain the highly varied clinical presentation. Further, WD is accompanied by structural and functional abnormalities in mitochondria, potentially altering the production of metabolites that are required for epigenetic regulation of gene expression. Notably, environmental exposure affects the regulation of gene expression and mitochondrial function. We present the “multi-hit” hypothesis of WD progression, which posits that the initial hit is an environmental factor that affects fetal gene expression and epigenetic mechanisms and subsequent “hits” are environmental exposures that occur in the offspring after birth. These environmental hits and subsequent changes in epigenetic regulation may impact copper accumulation and ultimately WD phenotype. Lifestyle changes, including diet, increased physical activity, stress reduction, and toxin avoidance, might influence the presentation and course of WD, and therefore may serve as potential adjunctive or replacement therapies.

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“…Later on, it was also found in immune cells, such as lymphocytes and monocytes [1,3]. It was stated that the three areas where BDNF is most active are the hippocampus, cortex, and basal forebrain [4,5]. Altered levels of BDNF, both in the circulating blood and in the CNS tissues, have been reported to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS) as well as in ischemic stroke [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The Relation of the Brain-Derived Neurotrophic Factor with MicroRNAs in Neurodegenerative Diseases and Ischemic Stroke

et al. 2020

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Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that plays a crucial role in the development of the nervous system while supporting the survival of existing neurons and instigating neurogenesis. Altered levels of BDNF, both in the circulation and in the central nervous system (CNS), have been reported to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), multiple sclerosis (MS), and ischemic stroke. MicroRNAs (miRNAs) are a class of non-coding RNAs found in body fluids such as peripheral blood and cerebrospinal fluid. Several different miRNAs, and their target genes, are recognized to be involved in the pathophysiology of neurodegenerative and neurovascular diseases. Thus, they present as promising biomarkers and a novel treatment approach for CNS disorders. Currently, limited studies provide viable evidence of miRNA-mediated post-transcriptional regulation of BDNF. The aim of this review is to provide a comprehensive assessment of the current knowledge regarding the potential diagnostic and prognostic values of miRNAs affecting BDNF expression and its role as a CNS disorders and neurovascular disease biomarker. Moreover, a novel therapeutic approach in neurodegenerative diseases and ischemic stroke targeting miRNAs associated with BDNF will be discussed.

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Influence of BDNF polymorphisms on Wilson’s disease susceptibility and clinical course

Cited by 8 publications

References 34 publications

Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease

Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

The Relation of the Brain-Derived Neurotrophic Factor with MicroRNAs in Neurodegenerative Diseases and Ischemic Stroke

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