Pharmacogenetics - The Year in Review.

S D Med. 2017 Dec;70(12):533-534

Authors: Lupu RA, Wilke RA

PMID: 29334439 [PubMed - in process]

Potential therapeutic and economic value of risk-stratified treatment as initial treatment of multiple myeloma in Europe.

Pharmacogenomics. 2018 Jan 15;:0

Authors: Gaultney JG, Ng TW, Uyl-de Groot CA, Sonneveld P, van Beers EH, van Vliet MH, Redekop WK

Abstract
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. Results suggest RST strategies were both cheaper and more effective than UT across all countries, with the molecular marker-only strategy RST-SKY92 producing maximum health gains (0.031-0.039 QALYs). The conclusions remained consistent in the univariate sensitivity analyses. These findings should encourage stakeholders to support the adoption of RST approaches in MM.

PMID: 29334316 [PubMed - as supplied by publisher]

miRNAs as potential regulators of mTOR pathway in renal cell carcinoma.

Pharmacogenomics. 2018 Jan 15;:

Authors: Nogueira I, Dias F, Teixeira AL, Medeiros R

Abstract
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. Several studies have described the involvement of miRNA dysregulation in the pathogenesis and progression of ccRCC. These molecules can be considered as potential diagnostic and prognostic biomarkers, allowing response to therapy to be monitored.

PMID: 29334302 [PubMed - as supplied by publisher]

Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

Am J Drug Alcohol Abuse. 2018 Jan 15;:1-10

Authors: Crist RC, Li J, Doyle GA, Gilbert A, Dechairo BM, Berrettini WH

Abstract
BACKGROUND: Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration.
OBJECTIVES: Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341).
METHODS: Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose.
RESULTS: Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone.
CONCLUSIONS: This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

PMID: 29333880 [PubMed - as supplied by publisher]

A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF.

Int J Med Sci. 2018;15(1):10-15

Authors: Romero-Cara P, Torres-Moreno D, Pedregosa J, Vílchez JA, García-Simón MS, Ruiz-Merino G, Morán-Sanchez S, Conesa-Zamora P

Abstract
BACKGROUND: The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance.
MATERIAL AND METHODS: A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured.
RESULTS: No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03).
CONCLUSION: FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients.

PMID: 29333082 [PubMed - in process]

ABCB1 C3435T gene polymorphism as a potential biomarker of clinical outcomes in HER2-positive breast cancer patients.

Pharmacol Res. 2016 Jun;108:111-118

Authors: Madrid-Paredes A, Cañadas-Garre M, Sánchez-Pozo A, Segura-Pérez AM, Chamorro-Santos C, Vergara-Alcaide E, Castillo-Portellano L, Calleja-Hernández MÁ

Abstract
HER2-positive breast cancer patients treated with trastuzumab schemes have good initial clinical outcomes. Despite this beneficial effect, many patients experiment resistance to these drugs. Several gene polymorphisms in ABCB1, HER2, and CCND1 have been proposed as potential predictors of clinical outcomes of trastuzumab schemes. The aim of this study was to evaluate the association between 4 gene polymorphisms potentially responsible for bad prognosis (HER2-Ile655Val, CCND1-A870G and ABCB1C1236T, C3435T) and clinical outcomes in HER2-positive BC patients. A retrospective cohorts study was performed. Eighty-four HER2-positive BC patients treated with trastuzumab schemes were included. The four gene polymorphisms were analyzed by PCR Real-Time with Taqman® probes. Genotypes were investigated for their association with tumor response, survival and resistance. Patients with CC genotype of ABCB1-C3435T presented higher risk of resistance to chemotherapy/trastuzumab schemes, compared to those carrying the T-allele (RR: 2.71; CI95%:1.29-5.68; p=0.013888), progression (RR: 1.89; p=0.017964); and exitus (RR: 2.09; p=0.03276). Multivariate logistic regression analysis considering clinical variables and ABCB1-C3435T revealed that the only independent factor associated to resistance to therapy was ABCB1-C3435T gene polymorphism (ORCT/CC: 0.25; p=0.0123; ORTT/CC: 0.09; p=0.0348. The protective effect of ABCB1-C3435T T-allele was confirmed in the multivariate Cox regression analysis for PFS (HRCT/CC: 0.41; p=0.00806; HRTT/CC: 0.22; p=0.01982) and OS (HRCT/CC: 0.49; p=0.0555; HRTT/CC: 0.12; p=0.0398). ABCB1-C1236T, CCND1-A870G and HER2-Ile655Val polymorphisms were not associated to resistance, PFS or OS (p>0.05). The A-allele for CCND1-rs9344 was associated with higher response rates (RR: 3.44; uncorrected p-value: 0.03816) in the bivariate analysis, but no statically association was found after Bonferroni correction (p=0.15264). ABCB1-C3435T, ABCB1-C1236T and HER2-Ile655Val gene polymorphisms were not associated with response. Although this study demonstrates a prognostic value of ABCB1-C3435T gene polymorphism to predict clinical outcomes, further studies with a larger sample will be necessary to validate this result.

PMID: 27137881 [PubMed - indexed for MEDLINE]

Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival.

Eur J Cancer. 2018 Jan 10;91:47-55

Authors: Dubot C, Bernard V, Sablin MP, Vacher S, Chemlali W, Schnitzler A, Pierron G, Ait Rais K, Bessoltane N, Jeannot E, Klijanienko J, Mariani O, Jouffroy T, Calugaru V, Hoffmann C, Lesnik M, Badois N, Berger F, Le Tourneau C, Kamal M, Bieche I

Abstract
BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value.
PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes.
RESULTS: A median of 2 (range: 0-10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis.
CONCLUSION: These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.

PMID: 29331751 [PubMed - as supplied by publisher]

Are Privacy-Enhancing Technologies for Genomic Data Ready for the Clinic? A Survey of Medical Experts of the Swiss HIV Cohort Study.

J Biomed Inform. 2018 Jan 10;:

Authors: Raisaro JL, McLaren PJ, Fellay J, Cavassini M, Klersy C, Hubaux JP, Swiss HIV Cohort Study

Abstract
PURPOSE: Protecting patient privacy is a major obstacle for the implementation of genomic-based medicine. Emerging privacy-enhancing technologies can become key enablers for managing sensitive genetic data. We studied physicians' attitude toward this kind of technology in order to derive insights that might foster their future adoption for clinical care.
METHODS: We conducted a questionnaire-based survey among 55 physicians of the Swiss HIV Cohort Study who tested the first implementation of a privacy-preserving model for delivering genomic test results. We evaluated their feedback on three different aspects of our model: clinical utility, ability to address privacy concerns and system usability.
RESULTS: 38/55 (69%) physicians participated in the study. Two thirds of them acknowledged genetic privacy as a key aspect that needs to be protected to help building patient trust and deploy new-generation medical information systems. All of them successfully used the tool for evaluating their patients' pharmacogenomics risk and 90% were happy with the user experience and the efficiency of the tool. Only 8% of physicians were unsatisfied with the level of information and wanted to have access to the patient's actual DNA sequence.
CONCLUSION: This survey, although limited in size, represents the first evaluation of privacy-preserving models for genomic-based medicine. It has allowed us to derive unique insights that will improve the design of these new systems in the future. In particular, we have observed that a clinical information system that uses homomorphic encryption to provide clinicians with risk information based on sensitive genetic test results can offer information that clinicians feel sufficient for their needs and appropriately respectful of patients' privacy. The ability of this kind of systems to ensure strong security and privacy guarantees and to provide some analytics on encrypted data has been assessed as a key enabler for the management of sensitive medical information in the near future. Providing clinically relevant information to physicians while protecting patients' privacy to comply with regulations is crucial for the widespread use of the new technologies.

PMID: 29331453 [PubMed - as supplied by publisher]

GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing.

Eur J Endocrinol. 2018 Jan 12;:

Authors: Maione L, Dwyer AA, Francou B, Guiochon-Mantel A, Binart N, Bouligand J, Young J

Abstract
Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are rare, related diseases that prevent normal pubertal development and cause infertility in affected men and women. However, the infertility carries a good prognosis as increasing numbers of patients with CHH/KS are now able to have children through medically assisted procreation. These are genetic diseases that can be transmitted to patients' offspring. Importantly patients and their families should be informed of this risk and given genetic counseling. CHH and KS are phenotypically and genetically heterogeneous diseases in which the risk of transmission largely depends on the gene(s) responsible(s). Inheritance may be classically Mendelian yet more complex, oligogenic modes of transmission have also been described. The prevalence of oligogenicity has risen dramatically since the advent of massively parallel next-generation sequencing (NGS) in which tens, hundreds or thousands of genes are sequenced at the same time. NGS is medically and economically more efficient and more rapid than traditional Sanger sequencing, and is increasingly being used in medical practice. Thus it seems plausible that oligogenic forms of CHH/KS will be increasingly identified making genetic counseling even more complex. In this context, the main challenge will be to differentiate true oligogenism from situations when several rare variants that do not have a clear phenotypic effect are identified by chance. This review aims to summarize the genetics of CHH/KS and to discuss the challenges of oligogenic transmission but also its role in incomplete penetrance and variable expresivity in a perspective of genetic counseling.

PMID: 29330225 [PubMed - as supplied by publisher]

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pharmacogenomics

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30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2018/01/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Precision medicine: does ethnicity information complement genotype-based prescribing decisions?

Ther Adv Drug Saf. 2018 Jan;9(1):45-62

Authors: Shah RR, Gaedigk A

Abstract
Inter-ethnic differences in drug response are all too well known. These are underpinned by a number of factors, including pharmacogenetic differences across various ethnic populations. Precision medicine relies on genotype-based prescribing decisions with the aim of maximizing efficacy and mitigating the risks. When there is no access to genotyping tests, ethnicity is frequently regarded as a proxy of the patient's probable genotype on the basis of overall population-based frequency of genetic variations in the ethnic group the patient belongs to, with some variations being ethnicity-specific. However, ever-increasing transcontinental migration of populations and the resulting admixing of populations have undermined the utility of self-identified ethnicity in predicting the genetic ancestry, and therefore the genotype, of the patient. An example of the relevance of genetic ancestry of a patient is the inadequate performance of European-derived pharmacogenetic dosing algorithms of warfarin in African Americans, Brazilians and Caribbean Hispanics. Consequently, genotyping a patient potentially requires testing for all known clinically actionable variants that the patient may harbour, and new variants that are likely to be identified using state-of the art next-generation sequencing-based methods. Furthermore, self-identified ethnicity is associated with a number of ethnicity-related attributes and non-genetic factors that potentially influence the risk of phenoconversion (genotype-phenotype discordance), which may adversely impact the success of genotype-based prescribing decisions. Therefore, while genotype-based prescribing decisions are important in implementing precision medicine, ethnicity should not be disregarded.

PMID: 29318005 [PubMed]

Perspective on the Genetic Response to Antiparasitics: A Review Article.

Iran J Parasitol. 2017 Oct-Dec;12(4):470-481

Authors: Alarcon-Valdes P, Ortiz-Reynoso M, Santillan-Benitez J

Abstract
Background: Drugs' pharmacokinetics and pharmacodynamics can be affected by diverse genetic variations, within which simple nucleotide polymorphisms (SNPs) are the most common. Genetic variability is one of the factors that could explain questions like why a given drug does not have the desired effect or why do adverse drug reactions arise.
Methods: In this retrospective observational study, literature search limits were set within PubMed database as well as the epidemiological bulletins published by the Mexican Ministry of Health, from Jan 1st 2001 to Mar 31st 2017 (16 years).
Results: Metabolism of antiparasitic drugs and their interindividual responses are mainly modified by variations in cytochrome P450 enzymes. These enzymes show high frequencies of polymorphic variability thus affecting the expression of CYP2C, CYP2A, CYP2A6, CYP2D6, CYP2E6 and CYP2A6 isoforms. Research in this field opens the door to new personalized treatment approaches in medicine.
Conclusion: Clinical and pharmacological utility yield by applying pharmacogenetics to antiparasitic treatments is not intended as a mean to improve the prescription process, but to select or exclude patients that could present adverse drug reactions as well as to evaluate genetic alterations which result in a diversity of responses, ultimately seeking to provide a more effective and safe treatment; therefore choosing a proper dose for the appropriate patient and the optimal treatment duration. Furthermore, pharmacogenetics assists in the development of vaccines. In other words, the aim of this discipline is to find therapeutic targets allowing personalized treatments.

PMID: 29317871 [PubMed]

Pharmacogenetic guidance: individualized medicine promotes enhanced pain outcomes.

J Pain Res. 2018;11:37-40

Authors: Dragic LL, Wegrzyn EL, Schatman ME, Fudin J

Abstract
The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain. The use of leucovorin in this patient decreased pain scores, which were clinically significant and increased functionality. This case demonstrates the importance of pharmacogenetics testing in patients, as this can help direct providers to better therapeutic options for their patients.

PMID: 29317847 [PubMed]

High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism.

PLoS One. 2018;13(1):e0190619

Authors: Vacher S, Castagnet P, Chemlali W, Lallemand F, Meseure D, Pocard M, Bieche I, Perrot-Applanat M

Abstract
Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP). The aim of this study was to identify the type of breast tumors (ERα-positive or ERα-negative) that express AHR and how AhR affects human tumorigenesis. The levels of AHR, AHR nuclear translocator (ARNT) and AHR repressor (AHRR) mRNA expression were analyzed in a cohort of 439 breast tumors, demonstrating a weak association between high AHR expression and age greater than fifty years and ERα-negative status, and HR-/ERBB2 breast cancer subtypes. AHRR mRNA expression was associated with metastasis-free survival, while AHR mRNA expression was not. Immunohistochemistry revealed the presence of AhR protein in both tumor cells (nucleus and/or cytoplasm) and the tumor microenvironment (including endothelial cells and lymphocytes). High AHR expression was correlated with high expression of several genes involved in signaling pathways related to inflammation (IL1B, IL6, TNF, IL8 and CXCR4), metabolism (IDO1 and TDO2 from the kynurenine pathway), invasion (MMP1, MMP2 and PLAU), and IGF signaling (IGF2R, IGF1R and TGFB1). Two well-known ligands for AHR (TCDD and BaP) induced mRNA expression of IL1B and IL6 in an ERα-negative breast tumor cell line. The breast cancer ER status likely influences AhR activity involved in these signaling pathways. The mechanisms involved in AhR activation and target gene expression in breast cancers are also discussed.

PMID: 29320557 [PubMed - in process]

Possible role of CYP2B6 genetic polymorphisms in ifosfamide-induced encephalopathy: report of three cases.

Fundam Clin Pharmacol. 2018 Jan 10;:

Authors: Duflot T, Marie-Cardine A, Verstuyft C, Filhon B, Pereira T, Guillemant NM, Joannidès R, Bellien J, Lamoureux F

Abstract
Ifosfamide (IFA) is a potent alkylating antitumoral agent but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In 3 consecutive cases of pediatric patients who exhibited ifosfamide-induced encephalopathy (IIE), genotyping of clinically relevant single nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed. Genetic investigations revealed the presence of CYP2B6 rs4803419 (C>T) in one patient while the two others carried the CYP2B6*6 allelic variant. All patients carried CYP3A4 wild type genotype (CYP3A4*1/*1). Because CYP2B6 deficient alleles may be responsible for an increased conversion of S-IFA into neurotoxic metabolites, screening for CYP2B6 polymorphisms may help to avoid IIE and improve clinical outcomes. This article is protected by copyright. All rights reserved.

PMID: 29319893 [PubMed - as supplied by publisher]

[Role of genetic markers in personalization of anti-angiogenic therapy in patients with exudative age-related macular degeneration].

Vestn Oftalmol. 2017;133(6):120-125

Authors: Moshetova LK, Sychev DA, Osmanova ER, Turkina KI

Abstract
The review presents data of clinical and pharmacogenetic research by Russian and foreign authors conducted within the last three years on the effectiveness of anti-angiogenic treatment against wet age-related macular degeneration (AMD). Scientific results on the association between angiogenesis-related gene polymorphisms responsible for predisposition to AMD on the one hand and a positive response to anti-VEGF therapy on the other are presented. Particular attention is paid to the main regulator of angiogenesis - the VEGF-A gene.

PMID: 29319678 [PubMed - in process]

Effect of genetic polymorphisms in SREBF-SCAP pathway on therapeutic response to rosuvastatin in Saudi metabolic syndrome patients.

Pharmacogenomics. 2018 Jan 10;:

Authors: Rafeeq MM, Habib HS, Murad HAS, Gari MA, Gazzaz ZJ

Abstract
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. Significant effect of SCAP (GG; B = -8.16, p = 0.001); SREBF-1a (GG; B = -7.47, p = 0.001) and SREBF-1a (-delG; B = -7.42, p = 0.001) was observed on total cholesterol reduction. Additive trend was found between SCAP genotypes and lipid reductions. A total of 88% responders have SCAP 'G' allele (p = 0.001). Patients carrying SCAP (GG) and SREBF-1a (GG and -delG) have 9.5-, 8.6- and 14.6-times more likelihood of being responders (p < 0.05). 'G' allele in SCAP and SREBF-1a is significant predictor of rosuvastatin response.

PMID: 29318930 [PubMed - as supplied by publisher]

The pharmacogenetics of medications used in general anesthesia.

Pharmacogenomics. 2018 Jan 10;:

Authors: Xie S, Ma W, Guo Q, Liu J, Li W, McLeod HL, He Y

Abstract
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.

PMID: 29318929 [PubMed - as supplied by publisher]

Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.

Pharmacogenomics. 2018 Jan 10;:

Authors: Oetting WS, Wu B, Schladt DP, Guan W, Remmel RP, Dorr C, Mannon RB, Matas AJ, Israni AK, Jacobson PA

Abstract
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.
RESULTS: Only variants in CYP3A4 and CYP3A5 were significantly associated with variation in TAC trough concentrations in our validation.
CONCLUSION: There is no evidence that common variants outside the CYP3A4 and CYP3A5 loci are associated with variation in TAC trough concentrations. In the future rare variants may be important and identified using DNA sequencing.

PMID: 29318894 [PubMed - as supplied by publisher]