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Pharmacogenomics

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https://www.readbyqxmd.com/read/29334316/potential-therapeutic-and-economic-value-of-risk-stratified-treatment-as-initial-treatment-of-multiple-myeloma-in-europe
#1
Jennifer G Gaultney, Therese W Ng, Carin A Uyl-de Groot, Pieter Sonneveld, Erik H van Beers, Martin H van Vliet, William K Redekop
Biomarkers associated with prognosis in multiple myeloma (MM) can be used to stratify patients into risk categories. An attractive alternative to uniform treatment (UT), risk-stratified treatment (RST) is proposed where high-risk patients receive bortezomib-based regimens while standard-risk patients receive alternative less costly regimens. An early Markov-type decision analytic model evaluated the potential therapeutic and economic value of different RST strategies compared with UT in MM patients in key European countries...
January 15, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29334302/mirnas-as-potential-regulators-of-mtor-pathway-in-renal-cell-carcinoma
#2
Inês Nogueira, Francisca Dias, Ana Luísa Teixeira, Rui Medeiros
Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the adult kidney with the majority of RCC cases being detected accidentally. The most aggressive subtype is clear cell RCC (ccRCC). miRNAs, a family of small noncoding RNAs regulating gene expression have been identified as key biological modulators. The von Hippel-Lindau pathway is one of the signaling pathways involved in the pathophysiology of ccRCC. Another oncogenic mechanism involves the activation of PI3K/AKT/mTOR signaling and serves as a central regulator of cell metabolism, proliferation and survival...
January 15, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29327975/impact-of-cyp2d6-on-venlafaxine-metabolism-in-trinidadian-patients-with-major-depressive-disorder
#3
Lazara Karelia Montané Jaime, Jeffrey Paul, Anthony Lalla, George Legall, Andrea Gaedigk
AIM: This study aimed to assess the impact of CYP2D6 and CYP2C19 variation on venlafaxine (VEN) at steady state in patients from Trinidad and Tobago of Indian and African descent with major depressive disorder. PATIENTS & METHODS: Patients were phenotyped with dextromethorphan, genotyped for CYP2D6 and CYP2C19, and metabolic ratios for VEN obtained at 2-week intervals. RESULTS: Of 61 patients, 55 were genotyped and phenotyped and 47 completed 8 weeks of VEN treatment...
January 12, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29327657/rare-disease-prevention-and-treatment-the-need-for-a-level-playing-field
#4
Dyfrig A Hughes, Catrin O Plumpton
Pharmacogenetic tests are being used increasingly to prevent rare and potentially life-threatening adverse drug reactions. For many tests, however, cost-effectiveness is hard to demonstrate, and with the exception of a few cases, widespread implementation remains a distant prospect. Many orphan drugs for rare diseases are also not cost effective but are nonetheless normally reimbursed. In this article, we argue that the health technology assessment of pharmacogenetic tests aimed to prevent rare but severe adverse drug reactions should be on a level playing field with orphan drugs...
January 12, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29325503/immunogenetics-of-prostate-cancer-a-still-unexplored-field-of-study
#5
Eva Dreussi, Fabrizio Ecca, Lucia Scarabel, Sara Gagno, Giuseppe Toffoli
The immune system is a double-edged sword with regard to the prostate cancer (PCa) battle. Immunogenetics, the study of the potential role of immune-related polymorphisms, is taking its first steps in the treatment of this malignancy. This review summarizes the most recent papers addressing the potential of immunogenetics in PCa, reporting immune-related polymorphisms associated with tumor aggressiveness, treatment toxicity and patients' prognosis. With some peculiarities, RNASEL, IL-6, IL-10, IL-1β and MMP7 have arisen as the most significant biomarkers in PCa treatment and management, having a potential clinical role...
January 12, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29325499/insights-and-barriers-to-clinical-use-of-serotonin-transporter-pharmacogenetics-in-antidepressant-therapy
#6
James M Stevenson
No abstract text is available yet for this article.
January 12, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29318930/effect-of-genetic-polymorphisms-in-srebf-scap-pathway-on-therapeutic-response-to-rosuvastatin-in-saudi-metabolic-syndrome-patients
#7
Misbahuddin Mohd Rafeeq, Hamed Said Habib, Hussam Aly Sayed Murad, Mamdouh Abdullah Gari, Zohair Jamil Gazzaz
AIM: Genetic variants contribute to statins' therapeutic variability. SREBF-SCAP pathway is a key player in lipid homeostasis. Hence, effect of SREBF-SCAP polymorphisms on therapeutic response was studied. PATIENTS & METHODS: Metabolic syndrome patients of either sex were prescribed rosuvastatin 10 mg for 24 weeks. Clinical, anthropometric and lipid measurements were done before and after treatment. Genotyping was done by pyrosequencing. RESULTS & CONCLUSION: No associations of SCAP and SREBF-1a genotypes with baseline lipids but significant associations with lipid reductions were observed...
January 10, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29318929/the-pharmacogenetics-of-medications-used-in-general-anesthesia
#8
Shangchen Xie, Wenjuan Ma, Qulian Guo, Jie Liu, Wei Li, Howard L McLeod, Yijing He
General anesthesia is a state of unconsciousness, amnesia, analgesia and akinesia induced by drugs including opioids, hypnotic-sedative agents, muscle relaxants and antiemetics. Clinical and genetic factors are reported to influence the efficacy and side effects of these agents. Based on the evidence, clinical action is needed to improve clinical outcomes. This review summarizes the latest knowledge with regards to the pharmacogenetics of anesthetics and general anesthesia related complications.
January 10, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29318894/attempted-validation-of-44-reported-snps-associated-with-tacrolimus-troughs-in-a-cohort-of-kidney-allograft-recipients
#9
William S Oetting, Baolin Wu, David P Schladt, Weihua Guan, Rory P Remmel, Casey Dorr, Roslyn B Mannon, Arthur J Matas, Ajay K Israni, Pamala A Jacobson
AIM: Multiple genetic variants have been associated with variation in tacrolimus (TAC) trough concentrations. Unfortunately, additional studies do not confirm these associations, leading one to question if a reported association is accurate and reliable. We attempted to validate 44 published variants associated with TAC trough concentrations. MATERIALS & METHODS: Genotypes of the variants in our cohort of 1923 kidney allograft recipients were associated with TAC trough concentrations...
January 10, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29239269/pharmacogenetic-landscape-of-dpyd-variants-in-south-asian-populations-by-integration-of-genome-scale-data
#10
Judith M Hariprakash, Shamsudheen K Vellarikkal, Pavithran Keechilat, Ankit Verma, Rijith Jayarajan, Vishal Dixit, Rowmika Ravi, Vigneshwar Senthivel, Anoop Kumar, Paras Sehgal, Akhilesh K Sonakar, Sakshi Ambawat, Anil K Giri, Arun Philip, Akhila Sivadas, Mohammed Faruq, Dwaipayan Bharadwaj, Sridhar Sivasubbu, Vinod Scaria
AIM: Adverse drug reactions to 5-Fluorouracil(5-FU) is frequent and largely attributable to genetic variations in the DPYD gene, a rate limiting enzyme that clears 5-FU. The study aims at understanding the pharmacogenetic landscape of DPYD variants in south Asian populations. MATERIALS & METHODS: Systematic analysis of population scale genome wide datasets of over 3000 south Asians was performed. Independent evaluation was performed in a small cohort of patients...
December 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29210335/predictive-role-of-nudt15-variants-on-thiopurine-induced-myelotoxicity-in-asian-inflammatory-bowel-disease-patients
#11
Natalia Sutiman, Sylvia Chen, Khoon Lin Ling, Sai Wei Chuah, Wai Fook Leong, Vinayak Nadiger, Madeline Tjai, Chris San Choon Kong, Brian John Schwender, Webber Chan, Hang Hock Shim, Wee Chian Lim, Chiea Chuen Khor, Yin Bun Cheung, Balram Chowbay
BACKGROUND: Genetic variants of TPMT and NUDT15 have been reported to predict the inter-patient variability in response and toxicity profiles of patients receiving thiopurine therapy. However, the clinical utility of TPMT genotyping in guiding thiopurine doses has been questionable, in part due to underlying differences in the prevalence of TPMT variants in both Caucasian and Asian populations. Several NUDT15 variants have been associated with thiopurine-induced leukopenia, particularly in Asian cohorts...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29210332/dopamine-gene-variants-in-opioid-addiction-comparison-of-dependent-patients-nondependent-users-and-healthy-controls
#12
Matthew Randesi, Wim van den Brink, Orna Levran, Vadim Yuferov, Peter Blanken, Jan M van Ree, Jurg Ott, Mary Jeanne Kreek
AIM: To determine whether specific dopaminergic system gene variants are associated with opioid dependence. PATIENTS & METHODS: Subjects included 153 healthy controls, 163 opioid exposed, but not dependent and 281 opioid dependent. Genotypes of 90 variants in 13 genes were examined. RESULTS: The most significant results were obtained for DA β-hydroxylase variants, rs2073837 and rs1611131, which were associated with protection from addiction (q = 0...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29210328/dna-variants-in-dhfr-gene-and-response-to-treatment-in-children-with-childhood-b-all-revisited-in-aieop-bfm-protocol
#13
Francesco Ceppi, Vincent Gagné, Laurance Douyon, Camille J Quintin, Antonella Colombini, Rosanna Parasole, Barbara Buldini, Giuseppe Basso, Valentino Conter, Giovanni Cazzaniga, Maja Krajinovic
AIM: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. METHODS: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29210323/effect-of-genetic-variation-in-ugt1a-and-abcb1-on-moxifloxacin-pharmacokinetics-in-south-african-patients-with-tuberculosis
#14
Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Helen McIlleron, Kogieleum Naidoo, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Mamoonah Chaudhry, Michael S Pepper, Nesri Padayatchi
AIM: We assessed the effect of genetic variability in UGT1A and ABCB1 genes on moxifloxacin pharmacokinetics. METHODS: Genotypes for selected UGT1A and ABCB1 SNPs were determined using a TaqMan® Genotyping OpenArray™ and high-resolution melt analysis for rs8175347. A nonlinear mixed-effects model was used to describe moxifloxacin pharmacokinetics. RESULTS: Genotypes of UGT1A SNPs, rs8175347 and rs3755319 (20.6% lower and 11.6% increased clearance, respectively) and ABCB1 SNP rs2032582 (40% reduced bioavailability in one individual) were significantly associated with changes in moxifloxacin pharmacokinetic parameters...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29210320/genetic-variation-in-statin-intolerance-and-a-possible-protective-role-for-ugt1a1
#15
Maria Alice V Willrich, Erin J Kaleta, Sandra C Bryant, Grant M Spears, Laura J Train, Sandra E Peterson, Vanda A Lennon, Stephen L Kopecky, Linnea M Baudhuin
The etiology of statin intolerance is hypothesized to be due to genetic variants that impact statin disposition and clearance. We sought to determine whether genetic variants were associated to statin intolerance. The studied cohort consisted of hyperlipidemic participants (n = 90) clinically diagnosed with statin intolerance by a cardiologist and matched controls without statin intolerance. Creatine kinase activity, lipid profiles and genetic analyses were performed on genes involved in statin metabolism and included UGT1A1 and UGT1A3 sequencing and targeted analyses of CYP3A4*22, CYP3A5*3, SLCO1B1*5 and *1b, ABCB1 c...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29207912/genome-wide-scan-identifies-candidate-loci-related-to-remifentanil-requirements-during-laparoscopic-assisted-colectomy
#16
Daisuke Nishizawa, Tsutomu Mieda, Miki Tsujita, Hideyuki Nakagawa, Shigeki Yamaguchi, Shinya Kasai, Junko Hasegawa, Ken-Ichi Fukuda, Akira Kitamura, Masakazu Hayashida, Kazutaka Ikeda
AIM:  Opioids are widely used as effective analgesics, but opioid sensitivity is well known to vary widely among individuals. We explored the genetic factors that contribute to individual differences in intraoperative opioid sensitivity by performing a genome-wide association study. PATIENTS & METHODS: We conducted a multistage genome-wide association study in subjects who underwent laparoscopic-assisted colectomy. RESULTS: A nonsynonymous SNP, rs199670311, within the TMEM8A gene region and intronic SNPs, including rs4839603, within the SLC9A9 gene region were significantly associated with intraoperative opioid requirements (p = 3...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29207898/nr3c1-gene-polymorphisms-are-associated-with-steroid-resistance-in-patients-with-primary-nephrotic-syndrome
#17
Jie Liu, Zan Wan, Qianqian Song, Zhi Li, Yijing He, Yongjun Tang, Wanying Xie, Yanyun Xie, Jun Zhang
AIM: The aim of this study was to investigate the role of SNPs of genes involved in the glucocorticoid pathway in the development of steroid resistance in patients with primary nephrotic syndrome. METHODS: Sequenom MassARRAY method was used to sequence 25 SNP genotypes in 154 patients. The frequency distribution of the genotypes was compared between patients with steroid-sensitive nephrotic syndrome and those with steroid-resistant nephrotic syndrome. RESULTS: NR3C1 rs6196 G allele carriers had a decreased risk of steroid resistance compared with that of the A allele carriers...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29199543/genetic-variations-of-the-xenoreceptors-nr1i2-and-nr1i3-and-their-effect-on-drug-disposition-and-response-variability
#18
Litaty Céphanoée Mbatchi, Jean-Paul Brouillet, Alexandre Evrard
NR1I2 (PXR) and NR1I3 (CAR) are nuclear receptors that are classified as xenoreceptors. Upon activation by various xenobiotics, including marketed drugs, they regulate the transcription level of major drug-metabolizing enzymes and transporters and facilitate the elimination of xenobiotics from the body. The modulation of the activity of these two xenoreceptors by various ligands is a major source of pharmacokinetic variability of environmental origin. NR1I2 and NR1I3 genetic polymorphisms can affect the pharmacokinetics and therapeutic response to many drugs, such as irinotecan, tacrolimus and atazanavir...
December 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29192552/polymorphisms-associated-with-adalimumab-and-infliximab-response-in-moderate-to-severe-plaque-psoriasis
#19
María C Ovejero-Benito, Rocío Prieto-Pérez, Mar Llamas-Velasco, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, María Talegón, Teresa Cabaleiro, Esteban Daudén, Francisco Abad-Santos
AIM: This study evaluated the influence of pharmacogenetics in psoriatic patients treated with adalimumab and/or infliximab. MATERIALS & METHODS: Prospective observational study evaluating the association of 124 polymorphisms with the response to adalimumab or infliximab (PASI75) in patients with moderate-to-severe plaque psoriasis at 3 months (n = 95) and 6 months of treatment (n = 90). Significant SNPs for univariate analysis were subjected to multivariate analysis...
December 1, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29191072/population-pharmacogenomics-impact-on-public-health-and-drug-development
#20
George P Patrinos
No abstract text is available yet for this article.
December 1, 2017: Pharmacogenomics
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