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Clinical pharmacogenetic models of treatment response to methotrexate monotherapy in Slovenian and Serbian rheumatoid arthritis patients : differences in patient's management may preclude generalization of the models
Jenko Bizjan, Barbara (Avtor), Tomšič, Matija (Avtor), Jekić, Biljana (Avtor), Milić, Vera (Avtor), Dolžan, Vita (Avtor), Praprotnik, Sonja (Avtor)

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Izvleček
Objectives: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but nevertheless 30% of patients experience MTX inefficacy. Our aim was to develop a clinical pharmacogenetic model to predict which RA patients will not respond to MTX monotherapy. We also assessed whether this model can be generalized to other populations by validating it on a group of Serbian RA patients. Methods: In 110 RA Slovenian patients, data on clinical factors and 34 polymorphisms in MTX pathway were analyzed by Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression to select variables associated with the disease activity as measured by Disease Activity Score (DAS28) score after 6 months of MTX monotherapy. A clinical pharmacogenetic index was constructed from penalized regression coefficients with absolute value above 0.05. This index was cross-validated and also independently validated on 133 Serbian RA patients. Results: A clinical pharmacogenetic index for prediction of DAS28 after 6 months of MTX monotherapy in Slovenian RA patients consisted of DAS28 score at diagnosis, presence of erosions, MTX dose, Solute Carrier Family 19 Member 1 (SLC19A1) rs1051266, Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) rs2306283, Thymidylate Synthase (TYMS), and Adenosine Monophosphate Deaminase 1 (AMPD1) rs17602729. It correctly classified 69% of Slovenian patients as responders or nonresponders and explained 30% of variability in DAS28 after 6 months of MTX monotherapy. Testing for validity in another population showed that it classified correctly only 22.5% of Serbian RA patients. Conclusions: We developed a clinical pharmacogenetic model for DAS28 after 6 months of MTX monotherapy in Slovenian RA patients by combining clinical and genetic variables. The clinical pharmacogenetic index developed for Slovenian patients did not perform well on Serbian patients, presumably due to the differences in patients' characteristics and clinical management between the two groups.

Jezik:Angleški jezik
Ključne besede:rheumatoid arthritis, pharmacogenetics, methotrexate, polymorphism, predictive model
Vrsta gradiva:Članek v reviji (dk_c)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:MF - Medicinska fakulteta
Leto izida:2018
Št. strani:8 str.
Številčenje:Vol. 9, art. 20
UDK:615
ISSN pri članku:1663-9812
DOI:10.3389/fphar.2018.00020 Povezava se odpre v novem oknu
COBISS.SI-ID:33649113 Povezava se odpre v novem oknu
Število ogledov:136
Število prenosov:39
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

Gradivo je financirano iz projekta

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

Financer:MESTD - Ministry of Education, Science and Technological Development of Republic of Serbia
Program financ.:Basic Research (BR or ON)
Številka projekta:175091
Naslov:The Analysis of Genetic Markers of Muscle Dystonia

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:25.01.2018

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:revmatoidni artritis, metotreksat, farmakogenetika, polimorfizem, napovedni model

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