@article{SteinMarufMuelleretal.2021,
  author    = {Stein, Kiera and Maruf, Abdullah Al and M{\"u}ller, Daniel J. and Bishop, Jeffrey R. and Bousman, Chad A.},
  title     = {Serotonin transporter genetic variation and antidepressant response and tolerability: a systematic review and meta-analysis},
  series = {Journal of Personalized Medicine},
  volume    = {11},
  journal   = {Journal of Personalized Medicine},
  number    = {12},
  issn      = {2075-4426},
  doi       = {10.3390/jpm11121334},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252294},
  year      = {2021},
  abstract  = {Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent.},
  language  = {en}
}
@article{JustSchollBoehmeetal.2021,
  author    = {Just, Katja S. and Scholl, Catharina and Boehme, Miriam and Kastenm{\"u}ller, Kathrin and Just, Johannes M. and Bleckwenn, Markus and Holdenrieder, Stefan and Meier, Florian and Weckbecker, Klaus and Stingl, Julia C.},
  title     = {Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (the IDrug randomized controlled trial) - never change a running system?},
  series = {Pharmaceuticals},
  volume    = {14},
  journal   = {Pharmaceuticals},
  number    = {10},
  issn      = {1424-8247},
  doi       = {10.3390/ph14101056},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248557},
  year      = {2021},
  abstract  = {The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with antithrombotic drugs in older adults. A randomized controlled trial was conducted in general practitioner (GP) offices. Patients aged 60 years and older, multi-morbid, taking antithrombotic drugs and at least one additional drug continuously were randomized to individualized and standardized risk assessment groups. Patients were followed up for nine months. A composite endpoint defined as at least one bleeding, thromboembolic event or death reported via a trigger list was used. Odds ratios (OR) and 95\% confidence intervals (CI) were calculated. In total, N = 340 patients were enrolled from 43 GP offices. Patients in the individualized risk assessment group met the composite endpoint more often than in the standardized group (OR 1.63 [95\%CI 1.02-2.63]) with multiple adjustments. The OR was higher in patients on phenprocoumon treatment (OR 1.99 [95\%CI 1.05-3.76]), and not significant on DOAC treatment (OR 1.52 [95\%CI 0.63-3.69]). Pharmacogenenetic variants of CYP2C9, 2C19 and VKORC1 were not observed to be associated with the composite endpoint. The results of this study may indicate that the time point for implementing individualized risk assessments is of importance.},
  language  = {en}
}
@article{ArimanyNardiMinuesaPastorAngladaetal.2016,
  author    = {Arimany-Nardi, Cristina and Minuesa, Gerard and Pastor-Anglada, Mar{\c{c}}al and Keller, Thorsten and Erkizia, Itziar and Koepsell, Hermann and Martinez-Picado, Javier},
  title     = {Role of Human Organic Cation Transporter 1 (hOCT1) Polymorphisms in Lamivudine (3TC) Uptake and Drug-Drug Interactions},
  series = {Frontiers in Pharmacology},
  volume    = {7},
  journal   = {Frontiers in Pharmacology},
  number    = {175},
  doi       = {10.3389/fphar.2016.00175},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165236},
  year      = {2016},
  abstract  = {Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level.},
  language  = {en}
}