The role of pharmacogenomics in the personalization of Parkinson's disease treatment

2020 ◽  
Vol 21 (14) ◽  
pp. 1033-1043
Author(s):  
Sara Redenšek ◽  
Vita Dolžan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Genetic Markers ◽  
Response To Treatment ◽  
Disease Treatment ◽  
Genetic Biomarkers ◽  
Genome Wide ◽  
Treatment Integration

Parkinson's disease (PD)-related phenotypes can vary among patients substantially, including response to dopaminergic treatment in terms of efficacy and occurrence of adverse events. Many pharmacogenetic studies have already been conducted to find genetic markers of response to dopaminergic treatment. Integration of genetic and clinical data has already resulted in construction of clinical pharmacogenetic models for prediction of adverse events. However, the results of pharmacogenetic studies are inconsistent. More comprehensive genome-wide approaches are needed to find genetic biomarkers of PD-related phenotypes to better explain the variability in response to treatment. These genetic markers should be integrated with clinical, environmental, imaging, and other omics data to build clinically useful algorithms for personalization of PD management.

scholarly journals Rural or urban living and Parkinson's disease

1996 ◽  
Vol 54 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Henrique B. Ferraz ◽  
Luiz A. F. Andrade ◽  
Vítor Tumas ◽  
Leandro C. Calia ◽  
Vanderci Borges
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rural Area ◽  
Living Environment ◽  
Response To Treatment ◽  
Urban Group ◽  
Determining Factor ◽  
Rural Group

Although the precise etiology of Parkinson's disease (PD) is as yet unknown, it appears that certain environmental factors are involved. Prior living in a rural area has been implicated as a possible risk factor for PD, particularly in the early onset type. We evaluated the role of previous living conditions in the clinical correlates and outcome characteristics of 118 PD patients. All of them were seen from January 1987 to October 1992. The Rural Group (RG) comprised 71 patients (60.2%) who had lived in the rural area for at least 10 years (mainly in early phase of life) and the Urban Group (UG) consisted of 47 patients (39.8%) who had lived their entire life in an urban environment. The average age at the beginning of the symptoms was 58.8 in the RG and 54.1 in the UG. The mixed form of the disease (tremor, rigidity and akinesia) was the most frequent in both groups. A minimum 6-month follow-up period was undertaken with 63 patients (average 20 months) and no difference in response to treatment or in progression of the illness was detected between the two groups. Our data show that the previous living environment does not appear to be a determining factor in either the clinical or outcome characteristics of PD.

scholarly journals DEFINING CANDIDATE PARKINSON’S DISEASE GENES THROUGH THE ANALYSIS OF GENOME-WIDE HOMOZYGOSITY

2020 ◽  
Author(s):  
Steven J Lubbe ◽  
Yvette C. Wong ◽  
Bernabe Bustos ◽  
Soojin Kim ◽  
Jana Vandrovcova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Autosomal Recessive Inheritance ◽  
Homozygosity Mapping ◽  
Disease Genes ◽  
Compound Heterozygous ◽  
Genome Wide ◽  
Biallelic Mutations ◽  
Functional Analyses

ABSTRACTEarly-onset Parkinson’s disease (EOPD) can be caused by biallelic mutations in PRKN, DJ1 and PINK1. However, while the identification of novel genes is becoming increasingly challenging, new insights into EOPD genetics have important relevance for understanding the pathways driving disease pathogenesis. Here, using extended runs of homozygosity (ROH) >8Mb as a marker for possible autosomal recessive inheritance, we identified 90 EOPD patients with extended ROH. Investigating rare, damaging homozygous variants to identify candidate genes for EOPD, 81 genes were prioritised. Through the assessment of biallelic (homozygous and compound heterozygous) variant frequencies in cases and controls from three independent cohorts totalling 3,381 PD patients and 2,463 controls, we identified two biallelic MIEF1 variant carriers among EOPD patients. We further investigated the role of disease-associated variants in MIEF1 which encodes for MID51, an outer mitochondrial membrane protein, and found that putative EOPD-associated variants in MID51 preferentially disrupted its oligomerization state. These findings provide further support for the role of mitochondrial dysfunction in the development of PD. Together, we have used genome-wide homozygosity mapping to identify potential EOPD genes, and future studies incorporating expanded datasets and further functional analyses will help to determine their roles in disease aetiology.

scholarly journals Exploring human-genome gut-microbiome interaction in Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zachary D. Wallen ◽  
William J. Stone ◽  
Stewart A. Factor ◽  
Eric Molho ◽  
Cyrus P. Zabetian ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Alpha Synuclein ◽  
Incomplete Penetrance ◽  
Susceptibility Loci ◽  
Opportunistic Pathogens ◽  
Host Genotype ◽  
Genome Wide

AbstractThe causes of complex diseases remain an enigma despite decades of epidemiologic research on environmental risks and genome-wide studies that have uncovered tens or hundreds of susceptibility loci for each disease. We hypothesize that the microbiome is the missing link. Genetic studies have shown that overexpression of alpha-synuclein, a key pathological protein in Parkinson’s disease (PD), can cause familial PD and variants at alpha-synuclein locus confer risk of idiopathic PD. Recently, dysbiosis of gut microbiome in PD was identified: altered abundances of three microbial clusters were found, one of which was composed of opportunistic pathogens. Using two large datasets, we found evidence that the overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus, and that the variants responsible modulate alpha-synuclein expression. Results put forth testable hypotheses on the role of gut microbiome in the pathogenesis of PD, the incomplete penetrance of PD susceptibility genes, and potential triggers of pathology in the gut.

scholarly journals Evaluation of the Role of LRRK2 Gene in Parkinson’s Disease in an East Indian Cohort

2012 ◽  
Vol 32 (6) ◽  
pp. 355-362 ◽  
Author(s):  
Tamal Sadhukhan ◽  
Mansi Vishal ◽  
Gautami Das ◽  
Aanchal Sharma ◽  
Arijit Mukhopadhyay ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Susceptibility Gene ◽  
East Indian ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
Lrrk2 Gene ◽  
East Indians ◽  
Gwa Studies

Leucine rich repeat kinase 2 (LRRK2)gene defects cause Parkinson's disease (PD). Recently,LRRK2has also been shown by genome wide association (GWA) studies to be a susceptibility gene for the disease. In India mutations inLRRK2is a rare cause of PD. We, therefore, genotyped 64 SNPs acrossLRRK2in 161 control samples and finally studied 6 haplotype tagging SNPs for association-based study on 300 cases and 446 ethnically matched controls to explore the potential role ofLRRK2as a susceptibility gene in PD for East Indians. We did not find any significant allele/ genotype or haplotype associations with PD suggesting that common genetic variants withinLRRK2play limited role in modulating PD among East Indians. In addition, we also screened for the common mutations (viz. p.R1441C, p.R1441G, p.R1441H, p.Y1699C, p.G2019S), and a risk variant common among Asians (p.G2385R) but did not observe any of the above mentioned variants in our cohort. Our study, therefore, strongly suggests thatLRRK2has minimal role as a candidate and susceptibility gene in PD pathogenesis among East Indians.

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