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Dopaminergic pathway genes influence adverse events related to dopaminergic treatment in Parkinson's disease
ID Redenšek Trampuž, Sara (Avtor), ID Flisar, Dušan (Avtor), ID Kojović, Maja (Avtor), ID Gregorič Kramberger, Milica (Avtor), ID Georgiev, Dejan (Avtor), ID Pirtošek, Zvezdan (Avtor), ID Trošt, Maja (Avtor), ID Dolžan, Vita (Avtor)

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Izvleček
Dopaminergic pathway is the most disrupted pathway in the pathogenesis of Parkinson's disease. Several studies reported associations of dopaminergic genes with the occurrence of adverse events of dopaminergic treatment. However, none of these studies adopted a pathway based approach. The aim of this study was to comprehensively evaluate the influence of selected single nucleotide polymorphisms of key dopaminergic pathway genes on the occurrence of motor and non-motor adverse events of dopaminergic treatment in Parkinson's disease. In total, 231 Parkinson's disease patients were enrolled. Demographic and clinical data were collected. Genotyping was performed for 16 single nucleotide polymorphisms from key dopaminergic pathway genes. Logistic and Cox regression analyses were used for evaluation. Results were adjusted for significant clinical data. We observed that carriers of at least one COMT rs165815 C allele had lower odds for developing visual hallucinations (OR = 0.34; 95% CI = 0.16-0.72; p = 0.004), while carriers of at least one DRD3 rs6280 C allele and CC homozygotes had higher odds for this adverse event (OR = 1.88; 95% CI = 1.00-3.54; p = 0.049 and OR = 3.31; 95% CI = 1.37-8.03; p = 0.008, respectively). Carriers of at least one DDC rs921451 C allele and CT heterozygotes had higher odds for orthostatic hypotension (OR = 1.86; 95% CI = 1.07-3.23; p = 0.028 and OR = 2.30; 95% CI = 1.26-4.20; p = 0.007, respectively). Heterozygotes for DDC rs3837091 and SLC22A1 rs628031 AA carriers also had higher odds for orthostatic hypotension (OR = 1.94; 95% CI = 1.07-3.51; p = 0.028 and OR = 2.57; 95% CI = 1.11-5.95; p = 0.028, respectively). Carriers of the SLC22A1 rs628031 AA genotype had higher odds for peripheral edema and impulse control disorders (OR = 4.00; 95% CI = 1.62-9.88; p = 0.003 and OR = 3.16; 95% CI = 1.03-9.72; p = 0.045, respectively). Finally, heterozygotes for SLC22A1 rs628031 and carriers of at least one SLC22A1 rs628031 A allele had lower odds for dyskinesia (OR = 0.48; 95% CI = 0.24-0.98, p = 0.043 and OR = 0.48; 95% CI = 0.25-0.92; p = 0.027, respectively). Gene-gene interactions, more specifically DDC-COMT, SLC18A2-SV2C, and SLC18A2-SLC6A3, also significantly influenced the occurrence of some adverse events. Additionally, haplotypes of COMT and SLC6A3 were associated with the occurrence of visual hallucinations (AT vs. GC: OR = 0.34; 95% CI = 0.16-0.72; p = 0.005) and orthostatic hypotension (ATG vs. ACG: OR = 2.48; 95% CI: 1.01-6.07; p = 0.047), respectively. Pathway based approach allowed us to identify new potential candidates for predictive biomarkers of adverse events of dopaminergic treatment in Parkinson's disease, which could contribute to treatment personalization.

Jezik:Angleški jezik
Ključne besede:Parkinson's disease, genetic polymorphism, dopaminergic pathway, personalized medicine, adverse events
Vrsta gradiva:Članek v reviji
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:MF - Medicinska fakulteta
Status objave pri reviji:Objavljeno
Verzija članka:Založnikova različica članka
Leto izida:2019
Št. strani:10 str.
Številčenje:Vol. 10, art. 8
PID:20.500.12556/RUL-128756 Povezava se odpre v novem oknu
UDK:615
ISSN pri članku:1663-9812
DOI:10.3389/fphar.2019.00008 Povezava se odpre v novem oknu
COBISS.SI-ID:34173401 Povezava se odpre v novem oknu
Datum objave v RUL:27.07.2021
Število ogledov:582
Število prenosov:136
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
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Gradivo je del revije

Naslov:Frontiers in pharmacology
Skrajšan naslov:Front. pharmacol.
Založnik:Frontiers Media
ISSN:1663-9812
COBISS.SI-ID:29551833 Povezava se odpre v novem oknu

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:28.01.2019

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:Parkinsonova bolezen, genetski polimorfizem, dopaminergično zdravljenje, personalizirana medicina, škodljivi dogodki

Projekti

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:P1-0170
Naslov:Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Program financ.:Grant for young researchers

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