https://hdl.handle.net/10259/11210 Sat, 11 Jul 2026 19:07:43 GMT 2026-07-11T19:07:43Z https://hdl.handle.net/10259/11910 Status of the implementation of pharmacogenetics in clinical practice in Spain: from regional to national initiatives Apellaniz-Ruiz, Maria; Barrachina, Jordi; Castro-Sanchez, Paula; Comes-Raga, Ana; García-González, Xandra; Gil-Rodriguez, Almudena; Lopez-Lopez, Elixabet; Maroñas, Olalla; Morón, Rocío; Muriel, Javier; Olivera, Gladys G.; Riera, Pau; Saiz-Rodríguez, Miriam; Salvador-Martín, Sara; Sans-Pola, Carla; Tejera-Pérez, Hugo; Velasco-Ruiz, Alejandro; Verde, Zoraida; Wang, Daniel; Rodríguez-Vicente, Ana E.; Nunez-Torres, Rocio Introduction: Pharmacogenetics (PGx) has the potential to improve patient care, allowing to transform medical interventions by providing personalized therapeutic strategies. Scientific evidence supports the use of PGx in clinical practice and international organizations are developing clinical guidelines to facilitate the utilization of PGx testing. However, clinical implementation of PGx is limited and unequal worldwide. Content: This review summarizes regional and national Spanish initiatives to implement PGx in the clinical practice. Summary and Outlook: Diverse strategies to implement PGx in healthcare are applied across countries or even in the different regions of a specific country. Such was the case of Spain, a European country with 17 Autonomous Regions and two Autonomous Cities, each onewith capacity tomanage their own healthcare systems. Nevertheless, during the past years, many initiatives and strategies have been launched in Spain to develop different aspects of PGx. Importantly, the National Healthcare System has approved a PGx testing catalogue. This review highlights the crucial work and efforts of scientific societies (like the Spanish Society of Pharmacogenetics and Pharmacogenomics), of experts in PGx, of healthcare providers and of governmental parties in the implementation of PGx to personalize patient therapy, focused in Spain. Sat, 01 Nov 2025 00:00:00 GMT https://hdl.handle.net/10259/11910 2025-11-01T00:00:00Z https://hdl.handle.net/10259/11909 The association between lifestyle factors and mortality in Huntington's disease Cubo Delgado, Esther; Rivadeneyra Posadas, Jéssica Jannett; Simón Vicente, Lucía; Aguado, Laura; Calvo Simal, Sara; Saiz Rodríguez, Miriam; Mariscal, Natividad; Muñoz-Siscart, Ignacio; Díaz-Piñeiro, Dolores; Miguel-Pérez, Irene; Gámez-Leyva, G.; García Bustillo, Álvaro; Martínez-Descalls, A. Introduction: Despite the wealth of evidence suggesting a protective role of lifestyle factors on Huntington’s disease (HD) onset and progression, their association with mortality has not been extensively studied. The aim of this study was to examine whether lifestyle factors such as caffeine and alcohol consumption, smoking, physical activity level, and Mediterranean diet (MeDi) adherence are associated with mortality among a Spanish cohort of patients with HD with a 9-year surveillance period. Methods: This national study was performed using a nested, observational, longitudinal design. We included subjects diagnosed with HD who participated in the European Huntington’s disease network and Enrol-HD studies. Date of death and baseline lifestyle factor information, demographics, disease severity assessed by the Unified Huntington’s Disease Rating Scale (UHDRS), Problem Behaviours Assessment, total functional capacity (TFC) scores, and comorbidities were collected. Adjusted Cox proportional hazards models were conducted to determine the association of lifestyle factors with mortality. Results: We included 87 patients (52 females) with a mean age of 48.62 ± 14.43 years and CAG repeats of 43.76 ± 5.92. Sixteen deaths were recorded. After correcting for multiple comparisons, deceased patients had higher UHDRS scores at baseline and lower caffeine consumption than live patients. In multivariate Cox regression models, after adjusting for age, CAG repeats, and TFC, mortality risk was associated with lower caffeine consumption (HR 0.13, 95% CI 0.04, 0.45). Tue, 01 Jul 2025 00:00:00 GMT https://hdl.handle.net/10259/11909 2025-07-01T00:00:00Z https://hdl.handle.net/10259/11908 Pharmacogenetic Biomarkers of Ibrutinib Response and Toxicity in Chronic Lymphocytic Leukemia: Insights from an Observational Study Pérez-Gómez, Noelia; Sanz-Solas, Antonio; Cuevas, Beatriz; Cuevas, María Victoria; Alonso-Madrigal, Cristina; Loscertales, Javier; Álvarez-Nuño, Rodolfo; García, Covadonga; Zubiaur, Pablo; Villapalos-García, Gonzalo; Parra-Garcés, Raúl Miguel; Mejía-Abril, Gina; Alcaraz, Raquel; Vinuesa, Raquel; Díaz-Gálvez, Francisco Javier; González-Oter, María; García-Sancha, Natalia; Azibeiro-Melchor, Raúl; González-López, Tomás José; Abad-Santos, Francisco; Labrador, Jorge; Saiz-Rodríguez, Miriam Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational study is to address interindividual variability in the efficacy and safety of ibrutinib treatment in 49 CLL patients. Methods: Genotyping of nine polymorphisms was performed by quantitative polymerase chain reaction (qPCR) using a ViiA7® PCR Instrument and TaqMan assays, and ibrutinib plasma concentrations were determined using high-performance liquid chromatography coupled to a tandem mass spectrometry detector (HPLC-MS/MS). Results: Our study confirmed a high response rate, with 62% of patients achieving complete remission (CR), 9% CR with incomplete hematologic recovery (CRi), and 24% partial remission (PR). The impact of genetic polymorphisms on the CR rate was evaluated, revealing no statistically significant associations for CYP3A4, CYP3A5, ABCB1, ABCG2, and SLCO1B1 variants. However, a tendency was observed for patients carrying ABCB1 rs1128503, rs1045642 T/T, or rs2032582 A/A genotypes to achieve a higher CR rate. Adverse drug reactions (ADRs) were frequent, with vascular disorders (39%) and infections (27%) being the most common. Genetic polymorphisms influenced ibrutinib toxicity, with CYP3A4 *1/*22 appearing to be protective against overall ADRs. Conclusions: The unexpected association between CYP3A4 *1/*22 genotype and lower ADR incidence, as well as the trend toward improved treatment response in patients carrying ABCB1 genotypes, suggests compensatory metabolic mechanisms. However, given the small sample size, larger studies are needed to confirm these findings and their clinical implications, while also aiming to uncover other non-genetic factors that may contribute to a better understanding of the variability in treatment response and toxicity. Tue, 01 Jul 2025 00:00:00 GMT https://hdl.handle.net/10259/11908 2025-07-01T00:00:00Z https://hdl.handle.net/10259/11907 Impact of Upper Limb Function on Activities of Daily Living and Quality of Life in Huntington’s Disease Simón Vicente, Lucía; Rivadeneyra Posadas, Jéssica Jannett; Mariscal, Natividad; Aguado, Laura; Miguel-Pérez, Irene; Saiz Rodríguez, Miriam; García Bustillo, Álvaro; Muñoz-Siscart, Ignacio; Díaz-Piñeiro, Dolores; Cubo Delgado, Esther Background/Objectives: Huntington’s disease (HD) is a neurodegenerative movement disorder associated with significant disability and impairment of Activities of Daily Living (ADLs). The impact of upper limb disability on quality of life (QoL) and its influence on ADLs is not well known yet. The aim of this study was to describe the manipulative dexterity, strength, and manual eye coordination of patients with manifest and premanifest-HD compared to healthy individuals and to analyze its influence on ADLs and QoL. Methods: We performed an observational, cross-sectional study including 71 ambulatory participants (27 manifest-HD patients, 15 premanifest-HD, and 29 controls). We gathered sociodemographic data, as well as clinical data, including cognition (MMSE), HD motor severity (Unified HD rating scale, UHDRS-TMS), QoL (Neuro-QoL), and ADLs (HD-ADL). Hand dexterity and strength in the dominant and non-dominant hand were assessed with the Nine Hole Peg Test, Ten Neurotest, Nut and Bolt Test, dynamometry, and Late-Life FDI. Analysis of covariance (ANCOVA) models were performed to investigate differences in hand function between manifest-HD, premanifest-HD, and controls. Results: Manifest-HD patients had significantly worse performance in manual and finger dexterity, fine-motor coordination, and poorer handgrip strength than premanifest-HD and controls. Premanifest-HD required more time to complete the test than controls. Significant correlations were found between hand variables and Late-Life FDI, Neuro-QoL, HD-ADL, and UHDRS-TMS. Conclusions: HD affects manipulative dexterity and hand function in premanifest and manifest patients. Therefore, to prevent disability and decreased QoL, evaluating the progression of upper limb dysfunction in HD is important to offer the best possible therapeutic interventions. Sun, 01 Dec 2024 00:00:00 GMT https://hdl.handle.net/10259/11907 2024-12-01T00:00:00Z