Effects of common functional MMP12 gene polymorphisms on PD in a Polish population

Białecka, Monika; Kurzawski, Mateusz; Vlaykova, Tatyana; Tacheva, Tanya; Dziedziejko, Violetta; Pierzchlińska, Anna; Droździk, Marek

doi:10.1016/j.pjnns.2017.06.001

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…The reported genetic associations between PDD and variants in A2M , TFAM (rs2306604), and UCHL1 (rs4861387) have not been replicated so far. Studies that investigated the genetic associations of PDD with variants in BDNF , CYP2D6 , IL‐10 , IL‐18 , MMP12 , NAT2 , PPARGC1A , PPARG , PSEN2 , RAGE , SLC6A4 , TOMM40 , and TREM2 have reported negative findings.…”

Section: Resultsmentioning

confidence: 99%

Systematic review of genetic association studies in people with Lewy body dementia

Sanghvi

Singh

Morrin

et al. 2020

Int J Geriat Psychiatry

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Objectives Lewy body dementia (LBD) causes more morbidity, disability, and earlier mortality than Alzheimer disease. Molecular mechanisms underlying neurodegeneration in LBD are poorly understood. We aimed to do a systematic review of all genetic association studies that investigated people with LBD for improving our understanding of LBD molecular genetics and for facilitating discovery of novel biomarkers and therapeutic targets for LBD. Methods We systematically reviewed five online databases (PROSPERO protocol: CRD42018087114) and completed the quality assessment using the quality of genetic association studies tool. Results Eight thousand five hundred twenty‐one articles were screened, and 75 articles were eligible to be included. Genetic associations of LBD with APOE, GBA, and SNCA variants have been replicated by two or more good quality studies. Our meta‐analyses confirmed that APOE‐ε4 is significantly associated with dementia with Lewy bodies (pooled odds ratio [POR] = 2.70; 95% CI, 2.37‐3.07; P < .001) and Parkinson's disease dementia (POR = 1.60; 95% CI, 1.21‐2.11; P = .001). Other reported genetic associations that need further replication include variants in A2M, BCHE‐K, BCL7C, CHRFAM7A, CNTN1, ESR1, GABRB3, MAPT, mitochondrial DNA (mtDNA) haplogroup H, NOS2A, PSEN1, SCARB2, TFAM, TREM2, and UCHL1. Conclusions The reported genetic associations and their potential interactions indicate the importance of α‐synuclein, amyloid, and tau pathology, autophagy lysosomal pathway, ubiquitin proteasome system, oxidative stress, and mitochondrial dysfunction in LBD. There is a need for larger genome‐wide association study (GWAS) for identifying more LBD‐associated genes. Future hypothesis‐driven studies should aim to replicate reported genetic associations of LBD and to explore their functional implications.

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Section: Resultsmentioning

confidence: 99%

Systematic review of genetic association studies in people with Lewy body dementia

Sanghvi

Singh

Morrin

et al. 2020

Int J Geriat Psychiatry

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“…They describe mutations in mitochondrial DNA and genes associated with the immune system or with dopamine metabolism. All pathways analysed in Polish populations are set out in Table 2 [57,58,[60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78].…”

Section: Other Genetic Analysis In Polandmentioning

confidence: 99%

“…One of these families is macrophage metalloelastase (MMP12), first identified as an elastolytic metalloproteinase secreted by inflammatory macrophages [82]. In 241 patients with PD, rs652438 G allele genotypes of MMP12 decreased the risk of the disease [65].…”

Section: Other Genetic Analysis In Polandmentioning

confidence: 99%

Genetics of Parkinson’s disease in the Polish population

Milanowski

Ross

Friedman

et al. 2021

Neurol Neurochir Pol.

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Introduction. Genetic forms of Parkinson's disease (PD) often cluster in different ethnic groups and may present with recognisable unique clinical manifestations. Our aim was to summarise the current state of knowledge regarding the genetic causes of PD and describe the first Polish patient with SNCA duplication.Methodology. We searched the electronic database, PubMed, for studies between January 1995 and June 2020 that evaluated genetics in Polish patients with PD, using the search terms 'Parkinson's disease, 'Polish' , 'genetics' , 'mutations' , and 'variants' .Results. In total, 73 publications were included in the review; 11 genes responsible for monogenic forms and 19 risk factor genes have been analysed in the Polish population. Pathogenic variants were reported in four monogenic genes (LRRK2, PRKN, PINK1, and SNCA). Eight genes were associated with PD risk in the Polish population (GBA, TFAM, NFE2L2, MMP12, HLA-DRA, COMT, MAOB, and DBH). Multiplex ligation-dependent probe amplification and Sanger sequencing in PRKN, PINK1, DJ1, LRRK2, and SNCA revealed SNCA duplication in a 43-year-old Polish patient with PD examined by movement disorder specialists. Conclusion.Only a limited number of positive results have been reported in genes previously associated with PD in the Polish population. In the era of personalised medicine, it is important to report on genetic findings in specific populations.

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Mitochondrial stress-induced H4K12 hyperacetylation dysregulates transcription in Parkinson’s disease

Huang,

Jin,

Anantharam

et al. 2024

Front. Cell. Neurosci.

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Aberrant epigenetic modification has been implicated in the pathogenesis of Parkinson’s disease (PD), which is characterized by the irreversible loss of dopaminergic (DAergic) neurons. However, the mechanistic landscape of histone acetylation (ac) in PD has yet to be fully explored. Herein, we mapped the proteomic acetylation profiling changes at core histones H4 and thus identified H4K12ac as a key epigenomic mark in dopaminergic neuronal cells as well as in MitoPark animal model of PD. Notably, the significantly elevated H4K12ac deposition in post-mortem PD brains highlights its clinical relevance to human PD. Increased histone acetyltransferase (HAT) activity and decreased histone deacetylase 2 (HDAC2) and HDAC4 were found in experimental PD cell models, suggesting the HAT/HDAC imbalance associated with mitochondrial stress. Following our delineation of the proteasome dysfunction that possibly contributes to H4K12ac deposition, we characterized the altered transcriptional profile and disease-associated pathways in the MitoPark mouse model of PD. Our study uncovers the axis of mitochondrial impairment-H4K12ac deposition-altered transcription/disease pathways as a neuroepigenetic mechanism underlying PD pathogenesis. These findings provide mechanistic information for the development of potential pharmacoepigenomic translational strategies for PD.

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Effects of common functional MMP12 gene polymorphisms on PD in a Polish population

Cited by 3 publications

References 32 publications

Systematic review of genetic association studies in people with Lewy body dementia

Systematic review of genetic association studies in people with Lewy body dementia

Genetics of Parkinson’s disease in the Polish population

Mitochondrial stress-induced H4K12 hyperacetylation dysregulates transcription in Parkinson’s disease

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