J Chemother. 2021 May 24:1-6. doi: 10.1080/1120009X.2021.1913702. Online ahead of print.

ABSTRACT

Ovarian cancer is the leading cause of death from gynecologic cancers, but platinum resistance remains a major obstacle in the chemotherapy of ovarian cancer. This study aims to examine the role of polymorphisms in sulfatase 1 (SULF1) in platinum resistance and survival in advanced epithelial ovarian cancer (EOC) patients. We genotyped 12 SNPs of SULF1 in 195 EOC patients treated with platinum using MassARRAY method and evaluated the association between the SNPs and platinum response. SULF1 rs3802278 was marginal significantly associated with platinum resistance in recessive model with p value of 0.055. The patients with SULF1 rs3802278 AA were more resistant to platinum-based chemotherapy comparing to those with AG/GG genotype (OR: 2.317, 95%CI: 0.982 ∼ 5.465). In survival analysis, rs3802278 was significantly associated with both of PFS and OS after adjusted by FIGO stage and age. Patients with AA genotypes showed a shorter PFS and OS than with AG/GG genotypes (median PFS: 15 months vs. 21 months, p = 0.010, HR = 1.876, 95%CI: 1.165-3.022; median OS: 42 months vs. 73 months, p = 0.031, HR = 1.928, 95%CI: 1.061-3.504). SULF1 rs3802278 may serve as a potential candidate biomarker for the prediction of platinum resistance and prognosis in Chinese EOC patients.

PMID:34029511 | DOI:10.1080/1120009X.2021.1913702

JHEP Rep. 2021 Mar 30;3(3):100284. doi: 10.1016/j.jhepr.2021.100284. eCollection 2021 Jun.

ABSTRACT

Fatty liver disease can be triggered by a combination of excess alcohol, dysmetabolism and other environmental cues, which can lead to steatohepatitis and can evolve to acute/chronic liver failure and hepatocellular carcinoma, especially in the presence of shared inherited determinants. The recent identification of the genetic causes of steatohepatitis is revealing new avenues for more effective risk stratification. Discovery of the mechanisms underpinning the detrimental effect of causal mutations has led to some breakthroughs in the comprehension of the pathophysiology of steatohepatitis. Thanks to this approach, hepatocellular fat accumulation, altered lipid droplet remodelling and lipotoxicity have now taken centre stage, while the role of adiposity and gut-liver axis alterations have been independently validated. This process could ignite a virtuous research cycle that, starting from human genomics, through omics approaches, molecular genetics and disease models, may lead to the development of new therapeutics targeted to patients at higher risk. Herein, we also review how this knowledge has been applied to: a) the study of the main PNPLA3 I148M risk variant, up to the stage of the first in-human therapeutic trials; b) highlight a role of MBOAT7 downregulation and lysophosphatidyl-inositol in steatohepatitis; c) identify IL-32 as a candidate mediator linking lipotoxicity to inflammation and liver disease. Although this precision medicine drug discovery pipeline is mainly being applied to non-alcoholic steatohepatitis, there is hope that successful products could be repurposed to treat alcohol-related liver disease as well.

PMID:34027340 | PMC:PMC8122117 | DOI:10.1016/j.jhepr.2021.100284

J Adv Res. 2020 Dec 7;30:147-158. doi: 10.1016/j.jare.2020.12.003. eCollection 2021 May.

ABSTRACT

INTRODUCTION: A population-specific genomic reference is important for research and clinical practice, yet it remains unavailable for Han Chinese (HC) in Taiwan.

OBJECTIVES: We report the first whole genome sequencing (WGS) database of HC (1000 Taiwanese genome (1KTW-WGS)) and demonstrate several applications to cardiovascular medicine.

METHODS: Whole genomes of 997 HC were sequenced to at least 30X depth. A total of 20,117 relatively healthy HC individuals were genotyped using a customized Axiom GWAS array. We performed a genome-wide genotype imputation technique using IMPUTE2.

RESULTS: We identified 26.7 million single-nucleotide variants (SNVs) and 4.2 million insertions-deletions. Of the SNVs, 16.1% were novel relative to dbSNP (build 152), and 34.2% were novel relative to gnomAD. A total of 18,450 healthy HC individuals were genotyped using a customized Genome-Wide Association Study (GWAS) array. We identified hypertension-associated variants and developed a hypertension prediction model based on the correlation between the WGS data and GWAS data (combined clinical and genetic models, AUC 0.887), and also identified 3 novel hyperlipidemia-associated variants. Each individual carried an average of 16.42 (SD = 3.72) disease-causing variants. Additionally, we established an online SCN5A (an important cardiac gene) database that can be used to explore racial differences. Finally, pharmacogenetics studies identified HC population-specific SNVs in genes (CYP2C9 and VKORC1) involved in drug metabolism and blood clotting.

CONCLUSION: This research demonstrates the benefits of constructing a population-specific genomic reference database for precision medicine.

PMID:34026292 | PMC:PMC8132201 | DOI:10.1016/j.jare.2020.12.003

Front Pharmacol. 2021 May 7;12:624104. doi: 10.3389/fphar.2021.624104. eCollection 2021.

ABSTRACT

Cytochrome P450 (CYP) 2D6 is a polymorphic enzyme expressed in the central nervous system (CNS), important in drug metabolism and with a potentially constitutive role in CNS function such as vigilance. This study aimed to analyze variability in CYP2D6 activity linked to vigilance-related adverse drug reactions (ADRs) in the CNS. A dataset of N = 2939 ADR cases of the prospective multicenter observational trial in emergency departments (EDs) (ADRED; trial registration: DRKS-ID: DRKS00008979) was analyzed. Dizziness as the most frequent reported CNS ADR symptom (12.7% of patients, n = 372) related to vigilance was chosen as the outcome. The association of dizziness with CYP2D6 activity markers was analyzed. The number of CYP2D6 substrates taken, a CYP2D6 saturation score (no, moderate, and strong saturation), a CYP2D6 saturation/inhibition score (no, weak, moderate, and strong), and composed CYP2D6 activity using a genotyped subsample (n = 740) calculating additive effects of genotype and CYP2D6 saturation by drug exposure were used as CYP2D6 activity markers. Effects were compared to other frequent nonvigilance-related CNS ADR symptoms (syncope and headache). Secondary analyses were conducted to control for other ADR symptoms frequently associated with dizziness (syncope, nausea, and falls). The majority of all patients (64.5%, n = 1895) took at least one drug metabolized by CYP2D6. Around a third took a CNS drug (32.5%, n = 955). The chance to present with drug-related dizziness to the ED increased with each CYP2D6 substrate taken by OR 1.11 [1.01-1.23]. Presenting with drug-related dizziness was more likely with CYP2D6 saturation and saturation/inhibition (both OR 1.27 [1.00-1.60]). The composed CYP2D6 activity was positively associated with dizziness (p = 0.028), while poorer activity affected patients more often with dizziness as an ADR. In contrast, nonvigilance-related ADR symptoms such as syncope and nausea were not consistently significantly associated with CYP2D6 activity markers. This study shows an association between the number of CYP2D6 substrates, the predicted CYP2D6 activity, and the occurrence of dizziness as a CNS ADR symptom. As dizziness is a vigilance-related CNS symptom, patients with low CYP2D6 activity might be more vulnerable to drug-related dizziness. This study underlines the need for understanding individual drug metabolism activity and individual risks for ADRs.

PMID:34025403 | PMC:PMC8138470 | DOI:10.3389/fphar.2021.624104

Dev Cogn Neurosci. 2021 May 17;49:100964. doi: 10.1016/j.dcn.2021.100964. Online ahead of print.

ABSTRACT

The concept of fetal consciousness is a widely discussed topic. In this study, we applied a hierarchical rule learning paradigm to investigate the possibility of fetal conscious processing during the last trimester of pregnancy. We used fetal magnetoencephalography, to assess fetal brain activity in 56 healthy fetuses between gestational week 25 and 40, during an auditory oddball paradigm containing first- and second-order regularities. The comparison of fetal brain responses towards standard and deviant tones revealed that the investigated fetuses show signs of hierarchical rule learning, and thus the formation of a memory trace for the second-order regularity. This ability develops over the course of the last trimester of gestation, in accordance with processes in physiological brain development and was only reliably present in fetuses older than week 35 of gestation. Analysis of fetal autonomic nervous system activity replicates findings in newborns, showing importance of activity state for cognitive processes. On the whole, our results support the assumption that fetuses in the last weeks of gestation are capable of consciously processing stimuli that reach them from outside the womb.

PMID:34023644 | DOI:10.1016/j.dcn.2021.100964

J Genet Genomics. 2021 Apr 14:S1673-8527(21)00084-9. doi: 10.1016/j.jgg.2021.03.007. Online ahead of print.

ABSTRACT

The response rate of most anti-cancer drugs is limited because of the high heterogeneity of cancer and the complex mechanism of drug action. Personalized treatment that stratifies patients into subgroups using molecular biomarkers is promising to improve clinical benefit. With the accumulation of preclinical models and advances in computational approaches of drug response prediction, pharmacogenomics has made great success over the last 20 years and is increasingly used in the clinical practice of personalized cancer medicine. In this article, we first summarize FDA-approved pharmacogenomic biomarkers and large-scale pharmacogenomic studies of preclinical cancer models such as patient-derived cell lines, organoids, and xenografts. Furthermore, we comprehensively review the recent developments of computational methods in drug response prediction, covering network, machine learning, and deep learning technologies and strategies to evaluate immunotherapy response. In the end, we discuss challenges and propose possible solutions for further improvement.

PMID:34023295 | DOI:10.1016/j.jgg.2021.03.007

Biochem Pharmacol. 2021 May 19:114616. doi: 10.1016/j.bcp.2021.114616. Online ahead of print.

ABSTRACT

BACKGROUND: Anthracycline are inhibitors of topoisomerase II leading to DNA double strand breaks, and it is widely used for treatment of breast cancer. eIF3a is the largest subunit of eukaryotic translation initiation factor 3 (eIF3) and highly expressed in breast cancer. In this study, we investigated the role of eIF3a in DSB DNA repair and the response of breast cancer patients to anthracycline-based chemotherapy.

METHODS: MTT assay was used to detect anthracycline sensitivity in cell lines. Real-time reverse transcriptase PCR, western blotting and immunofluorescence were performed to assess changes in gene expression levels. Cometassay and end-joining activity assay were conducted to explore the effect of eIF3a in NHEJ repair. Luciferase reporter assay was performed to detect LIG4 5'UTR activity. Immunohistochemistry was used to detect eIF3a, LIG4 and DNA-PKcs expression levels in breast cancer tissues.

RESULTS: The results showed that eIF3a increased cellular response to anthracyclines by regulating DSB repair activity via influencing the expression of LIG4 and DNA-PKcs at translational level. Breast cancer patients with high level of eIF3a or low level of LIG4 or low level of DNA-PKcs had better anthracycline-based chemotherapy prognosis compared. Moreover, Combined expressions of eIF3a, LIG4 and DNA-PKcs could be better to predict PFS in breast cancer patients with anthracycline-based chemotherapy.

CONCLUSION: our findings suggest that eIF3a effects anthracycline-based chemotherapy response by regulating DSB DNA repair.

PMID:34022189 | DOI:10.1016/j.bcp.2021.114616

NPJ Precis Oncol. 2021 May 21;5(1):43. doi: 10.1038/s41698-021-00177-0.

ABSTRACT

Sarcomas harboring EWSR1-NFATc2 fusions have historically been categorized and treated as Ewing sarcoma. Emerging evidence suggests unique molecular characteristics and chemotherapy sensitivities in EWSR1-NFATc2 fusion positive sarcomas. Comprehensive genomic profiles of 1024 EWSR1 fusion positive sarcomas, including 14 EWSR1-NFATc2 fusions, were identified in the FoundationCore® database. Additional data from the Gene Expression Omnibus, the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas datasets were included for analysis. EWSR1-NFATc2 fusion positive sarcomas were genomically distinct from traditional Ewing sarcoma and demonstrated upregulation of the mTOR pathway. We also present a case of a 58-year-old male patient with metastatic EWSR1-NFATc2 fusion positive sarcoma who achieved 47 months of disease stabilization when treated with combination mTOR and VEGF inhibition. EWSR1-NFATc2 fusion positive sarcomas are molecularly distinct entities with overactive mTOR signaling; which may be therapeutically targetable. These findings support the use of precision medicine in the Ewing family of tumors.

PMID:34021224 | DOI:10.1038/s41698-021-00177-0

Best Pract Res Clin Rheumatol. 2021 May 18:101691. doi: 10.1016/j.berh.2021.101691. Online ahead of print.

ABSTRACT

Psoriatic arthritis (PsA) is caused by a combination of environmental and multiple genetic factors, with clear evidence for a strong genetic basis. The remarkable accumulation of knowledge gained from genetic, pharmacogenetic, and therapeutic response of biologic agents in PsA has fundamentally changed and advanced our understanding of disease pathogenesis and has identified key signalling pathways. However, only one-quarter of the genetic contribution of PsA has been accounted for; and dissecting the genetic contributors of the cutaneous disease from those that would identify joint disease has been challenging. More importantly, the clinical utility of multiple proposed loci is unclear. In this review, we summarize the potential clinical relevance from established genetic associations and provide insight on the proposed molecular pathways that arise from these associations.

PMID:34020887 | DOI:10.1016/j.berh.2021.101691

Hum Immunol. 2021 May 18:S0198-8859(21)00111-7. doi: 10.1016/j.humimm.2021.04.009. Online ahead of print.

ABSTRACT

Inflammation promotes cancer development. To a large extent, this can be attributed to the recruitment of myeloid-derived suppressor cells (MDSCs) to tumors. These cells are known for establishing an immunosuppressive tumor microenvironment by suppressing T cell activities. However, MDSCs also promote metastasis and angiogenesis. Critically, as small non-coding RNAs that regulate gene expression, microRNAs (miRNAs) control MDSC activities. In this review, we discuss how miRNA networks regulate key MDSC signaling pathways, how they shape MDSC development, differentiation and activation, and how this impacts tumor development. By targeting the expression of miRNAs in MDSCs, we can alter their main signaling pathways. In turn, this can compromise their ability to promote multiple hallmarks of cancer. Therefore, this may represent a new powerful strategy for cancer immunotherapy.

PMID:34020831 | DOI:10.1016/j.humimm.2021.04.009

ESMO Open. 2021 May 18;6(3):100155. doi: 10.1016/j.esmoop.2021.100155. Online ahead of print.

ABSTRACT

Pancreatic cancer (PC) is a common cause of cancer-related death, due to difficulties in detecting early-stage disease, to its aggressive behaviour, and to poor response to systemic therapy. Therefore, developing strategies for early diagnosis of resectable PC is critical for improving survival. Diabetes mellitus is another major public health problem worldwide. Furthermore, diabetes can represent both a risk factor and a consequence of PC: nowadays, the relationship between these two diseases is considered a high priority for research. New-onset diabetes can be an early manifestation of PC, especially in a thin adult without a family history of diabetes. However, even if targeted screening for patients at higher risk of PC could be a promising approach, this is not recommended in asymptomatic adults with new-onset diabetes, due to the much higher incidence of hyperglycaemia than PC and to the lack of a safe and affordable PC screening test. Prompted by a well-established and productive multidisciplinary cooperation, the Italian Association of Medical Oncology (AIOM), the Italian Medical Diabetologists Association (AMD), the Italian Society of Endocrinology (SIE), and the Italian Society of Pharmacology (SIF) here review available evidence on the mechanisms linking diabetes and PC, addressing the feasibility of screening for early PC in patients with diabetes, and sharing a set of update statements with the aim of providing a state-of-the-art overview and a decision aid tool for daily clinical practice.

PMID:34020401 | DOI:10.1016/j.esmoop.2021.100155

Biomed Pharmacother. 2021 May 18;140:111735. doi: 10.1016/j.biopha.2021.111735. Online ahead of print.

ABSTRACT

Bark is the traditional medicinal component of Eucommia ulmoides Oliver (E. ulmoides). However, the demand for E. ulmoides medicinal materials seriously limits their sustainability. To alleviate resource constraints, the bioactivity of E. ulmoides leaves and its pharmacodynamic basis were investigated. In the present study, extracts of E. ulmoides leaves were found to display potential renal protective properties in rat glomerular mesangial (HBZY-1) cells treated with high levels of glucose, suggesting that they possess potential factors capable of treating diabetic nephropathy. Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to comprehensively characterize the chemical components of E. ulmoides leaves. A total of 83 possible chemical components, including 12 iridoids, 13 flavonoids, 14 lignans, 20 phenylpropanoids, 14 phenolic acids, and 10 additional components, were identified in E. ulmoides leaves. Network pharmacology was used for a preliminary exploration of the potential mechanism of action of renal protection afforded by E. ulmoides leaves towards diabetic nephropathy. The network pharmacology results were verified using a series of biological experiments. The present study provided the basis for the comprehensive development and utilization of E. ulmoides leaves and the discovery of potential drugs.

PMID:34020251 | DOI:10.1016/j.biopha.2021.111735

J Mol Diagn. 2021 May 18:S1525-1578(21)00121-5. doi: 10.1016/j.jmoldx.2021.04.012. Online ahead of print.

ABSTRACT

Pharmacogenetic (PGx) testing is increasingly available from clinical and research laboratories. However, only a limited number of quality control and other reference materials (RMs) are currently available for many of the variants that are tested. The Association for Molecular Pathology PGx Work Group has published a series of papers recommending alleles for inclusion in clinical testing. Several of the alleles were not considered for Tier 1 due to a lack of reference materials. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention (CDC) based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 18 DNA samples derived from Coriell cell lines. DNA samples were distributed to five volunteer testing laboratories for genotyping using three commercially available and laboratory developed tests. Several Tier 2 variants including CYP2C9*13, CYP2C19*35, the CYP2C cluster variant (rs12777823), two variants in VKORC1 (rs61742245 and rs72547529) related to warfarin resistance and two variants in GGCX (rs12714145 and rs11676382) related to clotting factor activation were identified among these samples. These publicly available materials complement the pharmacogenetic reference materials previously characterized by GeT-RM and will support the quality assurance and quality control programs of clinical laboratories performing pharmacogenetic testing.

PMID:34020041 | DOI:10.1016/j.jmoldx.2021.04.012

Cancer Cell. 2021 May 7:S1535-6108(21)00221-X. doi: 10.1016/j.ccell.2021.04.013. Online ahead of print.

NO ABSTRACT

PMID:34019805 | DOI:10.1016/j.ccell.2021.04.013

PLoS Pathog. 2021 May 21;17(5):e1009577. doi: 10.1371/journal.ppat.1009577. Online ahead of print.

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes an aggressive T-cell malignancy and a variety of inflammatory conditions. The integrated provirus includes a single binding site for the epigenomic insulator, CCCTC-binding protein (CTCF), but its function remains unclear. In the current study, a mutant virus was examined that eliminates the CTCF-binding site. The mutation did not disrupt the kinetics and levels of virus gene expression, or establishment of or reactivation from latency. However, the mutation disrupted the epigenetic barrier function, resulting in enhanced DNA CpG methylation downstream of the CTCF binding site on both strands of the integrated provirus and H3K4me3, H3K36me3, and H3K27me3 chromatin modifications both up- and downstream of the site. A majority of clonal cell lines infected with wild type HTLV-1 exhibited increased plus strand gene expression with CTCF knockdown, while expression in mutant HTLV-1 clonal lines was unaffected. These findings indicate that CTCF binding regulates HTLV-1 gene expression, DNA and histone methylation in an integration site dependent fashion.

PMID:34019588 | DOI:10.1371/journal.ppat.1009577

Pharmacogenomics. 2021 May 21. doi: 10.2217/pgs-2020-0157. Online ahead of print.

ABSTRACT

Major depressive disorder is connected with high rates of functional disability and mortality. About a third of the patients are at risk of therapy failure. Several pharmacogenetic markers especially located in CYP450 genes such as CYP2D6 or CYP2C19 are of relevance for therapy outcome prediction in major depressive disorder but a further optimization of predictive tools is warranted. The article summarizes the current knowledge on pharmacogenetic variants, therapy effects and side effects of important antidepressive therapeutics, and sheds light on new methodological approaches for therapy response estimation based on genetic markers with relevance for pharmacokinetics, pharmacodynamics and disease pathology identified in genome-wide association study analyses, highlighting polygenic risk score analysis as a tool for further optimization of individualized therapy outcome prediction.

PMID:34018822 | DOI:10.2217/pgs-2020-0157

Front Immunol. 2021 May 4;12:661135. doi: 10.3389/fimmu.2021.661135. eCollection 2021.

ABSTRACT

HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67-198.21, p = 5.3447 × 10-7), SJS-TEN (OR = 36.00, 95% CI = 3.19-405.89, p = 2.1657 × 10-3), and DRESS (OR = 40.50, 95% CI = 6.38-257.03, p = 1.0784 × 10-5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67-149.52, p = 2.8068 × 10-7) and Taiwanese (OR = 31.50, 95% CI = 4.80-206.56, p = 2.5519 × 10-3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.

PMID:34017337 | PMC:PMC8130671 | DOI:10.3389/fimmu.2021.661135

Nat Commun. 2021 May 20;12(1):3165. doi: 10.1038/s41467-021-23648-1.

NO ABSTRACT

PMID:34016983 | DOI:10.1038/s41467-021-23648-1

Sr Care Pharm. 2021 Jun 1;36(6):304-310. doi: 10.4140/TCP.n.2021.304.

ABSTRACT

OBJECTIVE: To report a case of chronic anticholinergic toxicity in a referred, pharmacogenomics (PGx), polypharmacy patient.

SUMMARY: The patient is a 67-year-old male who was referred to the polypharmacy service for a PGx consult. This patient has had episodic fever of unknown origin, general cutaneous vasodilation, tremors, jerks, and brain fogginess which have been unexplained. He has seen specialists from infectious disease, rheumatology, endocrinology, and neurology with no contributory condition causing these symptoms, so he was referred for PGx testing and evaluation by the polypharmacy pharmacist.

CONCLUSION: This case demonstrates the importance of pharmacist-patient consultations and how a PGx consult may expose polypharmacy medicationrelated problems of greater significance than the PGx indication for the consult. In addition, the case demonstrates positive interprofessional collaboration between pharmacists and physicians to more effectively solve complex medication-related problems that may not be easily diagnosed through objective lab or diagnostic testing.

PMID:34016227 | DOI:10.4140/TCP.n.2021.304

Sr Care Pharm. 2021 Jun 1;36(6):276-282. doi: 10.4140/TCP.n.2021.276.

ABSTRACT

Major depressive disorder (MDD) is a mood disorder common in older individuals. While many clinical guidelines endorse the use of selective serotonin reuptake inhibitors (SSRIs) as first-line therapy in the treatment of MDD, the use of SSRIs in older populations can result in medication-related adverse events. The use of pharmacogenomic (PGx) testing as a personalized tool to determine optimal SSRI therapy could offer a means to decrease morbidity and improve overall quality of life in older people. This manuscript will review the epidemiology and criteria of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), discuss the prevalence of MDD in older individuals, review the clinical treatment guidelines for the use of SSRIs in MDD, provide a brief overview of PGx testing, and present evidence for SSRI therapy modifications based on PGx testing.

PMID:34016225 | DOI:10.4140/TCP.n.2021.276