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pharmacogenomics

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18 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 2020/05/19

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.

Neonatal diabetes due to potassium channel mutation: response to sulfonylurea according to the genotype.

Pediatr Diabetes. 2020 May 16;:

Authors: Garcin L, Mericq V, Fauret-Amsellem AL, Cave H, Polak M, Beltrand J

Abstract
OBJECTIVE: A precision medicine approach is used to improve treatment of patients with monogenic diabetes. Herein we searched SU efficiency according to the genotype-phenotype correlation, dosage used and side effects.
RESEARCH DESIGN AND METHODS: Systematic review conducted according the PRISMA control criteria identifying relevant studies evaluating the in vivo and in vitro sensitivity of ATP-dependent potassium channels according to the characteristics of genetic mutation.
RESULTS: 103 selected articles with complete data in 502 cases in whom 413 (82.3%) had mutations in KCNJ11 (#64) and 89 in ABCC8 (# 56). Successful transfer from insulin to SU was achieved in 91% and 86.5% patients, respectively at a mean age of 36.5 months (0-63 years). Among patients with KCNJ11 and ABCC8 mutations 64 & 46 were associated with constant success,5 & 5 to constant failure, and 10 and 4 to variable degrees of reported success rate, respectively. The glibenclamide dosage required for each genotype ranged from 0.017 to 2.8 mg / kg / day. Comparing both the in vivo and in vitro susceptibility results, some mutations appear more sensitive than others to sulfonylurea treatment. Side effects were reported in 17 /103 of the included articles: mild gastrointestinal symptoms and hypoglycaemia were the most common. One premature patient had an ulcerative necrotizing enterocolitis which association with SU is difficult to ascertain.
CONCLUSIONS: Sulfonylurea are an effective treatment for monogenic diabetes due to KCNJ11 and ABCC8 genes mutations. The success of the treatment is conditioned by differences in pharmacogenetics, younger age, pharmacokinetics, compliance and maximal dose used. This article is protected by copyright. All rights reserved.

PMID: 32418263 [PubMed - as supplied by publisher]

Propranolol suppresses the growth of colorectal cancer through simultaneously activating autologous CD8+ T cells and inhibiting tumor AKT/MAPK pathway.

Clin Pharmacol Ther. 2020 May 17;:

Authors: Liao P, Song K, Zhu Z, Liu Z, Zhang W, Li W, Hu J, Hu Q, Chen C, Chen B, McLeod HL, Pei H, Chen L, He Y

Abstract
Propranolol suppresses tumor growth in a variety of preclinical solid tumor models, with a number of proposed cell signaling and immunological mechanisms. We want to confirm the potential mechanisms, including reduced phosphorylation of AKT/MAPK pathways, as well as enhanced CD8+ T-cell-mediated antitumor immune response. To clarify the mechanism of propranolol activity in colorectal cancer, the therapeutic activity of propranolol was then assessed in CT26WT tumors engrafted in BALB/C mice. Then the effect of propranolol treatment was also examined by randomizing patients undergoing surgical resection of a previously untreated colorectal cancer to propranolol or placebo group and treated for 1 week prior to surgery. CT26WT tumor size was smaller after propranolol than vehicle control. Propranolol downregulated the expression of p-AKT/p-ERK/p-MEK in tumor tissue. The frequency of tumor CD8+ T cells was significantly elevated in propranolol-treated mice. The expression of GzmB/IFN-γ/T-bet in the CD8+ T-cell population was significantly increased in propranolol treated mice tumor tissue. In propranolol-treated surgical specimens, the expression of p-ERK was decreased and the frequency of CD8+ was significantly elevated. The expression of GzmB in the CD8+ T-cell population was significantly increased in propranolol-treated subjects. Together these data show propranolol simultaneously activating autologous CD8+ T cells and decreasing the expression of p-AKT/p-ERK/p-MEK in mouse tumor models, while inhibiting the expression of p-ERK in clinical colorectal cancer. Effort is now needed to further dissect whether both pathways are required for anti-tumor effect, as the activity of this old drug is moved forward.

PMID: 32418204 [PubMed - as supplied by publisher]

Effect of Cytochrome P450 and ABCB1 Polymorphisms on Imatinib Pharmacokinetics After Single-Dose Administration to Healthy Subjects.

Clin Drug Investig. 2020 May 15;:

Authors: Pena MÁ, Muriel J, Saiz-Rodríguez M, Borobia AM, Abad-Santos F, Frías J, Peiró AM

Abstract
BACKGROUND: Validated genomic biomarkers for oncological drugs are expanding to improve targeted therapies. Pharmacogenetics research focusing on the mechanisms underlying imatinib suboptimal response might help to explain the different treatment outcomes and drug safety profiles.
OBJECTIVE: To investigate whether polymorphisms in genes encoding cytochrome P450 (CYP) enzymes and ABCB1 transporter affect imatinib pharmacokinetic parameters.
METHODS: A prospective, multicenter, pharmacogenetic pilot study was performed in the context of two separate oral imatinib bioequivalence clinical trials, which included 26 healthy volunteers. DNA was extracted in order to analyze polymorphisms in genes CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and ABCB1. Imatinib plasma concentrations were measured by HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods using WinNonlin software.
RESULTS: Volunteers (n = 26; aged 24 ± 3 years; 69% male) presented regular pharmacokinetic imatinib data (concentration at 24 h, 436 ± 140 ng/mL and at 72 h, 40 ± 26 ng/mL; AUC0-72 32,868 ± 10,713 ng/mL⋅h; and Cmax 2074 ± 604 ng/mL). CYP2B6 516GT carriers showed a significant reduction of imatinib concentration at 24 h (23%, 391 ng/dL vs 511 ng/dL in 516GG carriers, p = 0.005) and elimination half-life (11%, 12.6 h vs 14.1 h in 516GG carriers, p = 0.041). Carriers for CYP3A4 (*22/*22, *1/*20 and *1/*22 variants) showed a reduced frequency of adverse events compared to *1/*1 carriers (0 vs 64%, p = 0.033). The other polymorphisms analyzed did not influence pharmacokinetics or drug toxicity.
CONCLUSION: CYP2B6 G516T and CYP3A4 *20,*22 polymorphisms could influence imatinib plasma concentrations and safety profile, after single-dose administration to healthy subjects. This finding needs to be confirmed before it is implemented in clinical practice in oncological patients under treatment with imatinib.

PMID: 32415468 [PubMed - as supplied by publisher]

A Multimodal Genotoxic Anti-cancer Drug Characterized by Pharmacogenetic Analysis in Caenorhabditis elegans.

Genetics. 2020 May 15;:

Authors: Ye FB, Hamza A, Singh T, Flibotte S, Hieter P, O'Neil NJ

Abstract
New anti-cancer therapeutics require extensive in vivo characterization to identify endogenous and exogenous factors affecting efficacy, to measure toxicity and mutagenicity, and to determine genotypes that result in therapeutic sensitivity or resistance. We used Caenorhabditis elegans as a platform with which to characterize properties of the anti-cancer therapeutic CX-5461. To understand the processes that respond to CX-5461-induced damage, we generated pharmacogenetic profiles for panel of C. elegans DNA replication and repair mutants with common DNA damaging agents to compare to the profile of CX-5461. We found that multiple repair pathways, including homology directed repair, microhomology-mediated end joining, nucleotide excision repair, and translesion synthesis, were needed for CX-5461 tolerance. To determine the frequency and spectrum of CX-5461-induced mutations, we used a genetic balancer to capture CX-5461-induced mutations. We found that CX-5461 is mutagenic, resulting in both large copy number variations and a high frequency of single nucleotide variations (SNVs), which are consistent with the pharmacogenetic profile for CX-5461. Whole genome sequencing of CX-5461 exposed animals found that CX-5461-induced SNVs exhibited a distinct mutational signature. We also phenocopied the CX-5461 photo-reactivity observed in clinical trials and demonstrated that CX-5461 generates reactive oxygen species when exposed to UVA radiation. Together, the data from C. elegans demonstrate that CX-5461 is a multimodal DNA damaging anti-cancer agent.

PMID: 32414869 [PubMed - as supplied by publisher]

GSTM1 null variant associated with anthracycline-related cancer in pediatric cancer.

Cancer. 2020 May 15;:

Authors: Rassekh SR

PMID: 32413168 [PubMed - as supplied by publisher]

EHD2 is a Predictive Biomarker of Chemotherapy Efficacy in Triple Negative Breast Carcinoma.

Sci Rep. 2020 May 14;10(1):7998

Authors: Shen WW, Bièche I, Fuhrmann L, Vacher S, Vincent-Salomon A, Torrino S, Lamaze C

Abstract
EHD2 is a mechanotransducing ATPase localized in caveolae invaginations at the plasma membrane. EHD2 has recently been associated with several human cancers, however the significance of EHD2 transcript levels in cancer prognosis remains debated. Breast cancer is the most commonly occurring cancer in women and prognosis is variable depending on the subtypes. Triple negative breast cancer (TNBC) often has a poor therapeutic response. The aim of this study was to assess the prognostic significance of EHD2 transcripts and protein expression levels in breast carcinomas. We found that low EHD2 levels were associated with enhanced proliferation, migration and invasion of TNBC cells. EHD2 expression was significantly reduced in TNBC tissues and the loss of EHD2 led to higher expression of the pro-tumoral cytokine IL-8. In apparent contradiction with in vitro data, multivariate analysis of two independent cohorts of breast cancer patients revealed that low EHD2 was in fact associated with good prognosis in the highly proliferative TNBC subtype. Accordingly, TNBC low EHD2 expressers were found to benefit the most from chemotherapy when compared to all subtypes of breast cancers. Our study validates EHD2 expression level as an independent prognostic factor of metastasis-free survival and as a new predictive marker of chemotherapy efficacy in TNBC patients.

PMID: 32409676 [PubMed - in process]

An Exploratory Analysis on the Influence of Genetic Variants on Weight Gain among Etonogestrel Contraceptive Implant Users.

Contraception. 2020 May 11;:

Authors: Lazorwitz A, Dindinger E, Harrison M, Aquilante CL, Sheeder J, Teal S

Abstract
OBJECTIVE: To identify genetic variants associated with weight gain related to etonogestrel contraceptive implant use.
STUDY DESIGN: We conducted a retrospective analysis from a parent pharmacogenomic study of healthy, reproductive-aged women using etonogestrel implants. We reviewed medical records to calculate objective weight changes from implant insertion to study enrollment and asked participants about subjective weight gain (yes/no) during contraceptive implant use. We used genotyping data (99 genetic variants) from the parent study to conduct backward-stepwise generalized linear modeling to identify genetic variants associated with objective weight changes.
RESULTS: Among 276 ethnically diverse participants, median body-mass index (BMI) was 25.8kg/m2 (range 18.5-48.1). We found a median weight change of +3.2kg (range -27.6 to +26.5) from implant insertion to study enrollment. Report of subjective weight gain had minimal agreement with measured weight gain during implant use (Cohen's kappa=0.21). Our final generalized linear model contained two variables associated with objective weight change that met conservative statistical significance (p<5.0x10-4). Participants with two copies (homozygous) of the ESR1 rs9340799 variant on average gained 14.1kg more than all other participants (p=1.4x10-4). Higher enrollment BMI was also associated with objective weight gain (β= 0.54, p=9.4x10-12).
CONCLUSION: Genetic variants in the estrogen receptor 1 (ESR1) do not have known associations with obesity or metabolic syndrome, but there is physiologic plausibility for a progestin-mediated genetic association between ESR1 and weight gain. Additional genetic research is needed to substantiate our findings and elucidate further advances in individualized counseling on the risk of weight gain with exogenous steroid hormones.
IMPLICATIONS: Genetic variation in the estrogen receptor 1 gene may account for variability in weight gain among etonogestrel contraceptive implant users. If these findings can be replicated with other progestin-containing medications, we may be able to better individualize contraceptive counseling.

PMID: 32407811 [PubMed - as supplied by publisher]

Ifosfamide and etoposide in advanced-stage, relapsed or refractory primary cutaneous T-cell lymphomas.

Br J Dermatol. 2020 May 14;:

Authors: Dangien A, Ram-Wolff C, Brice P, Battistella M, Roelens M, Moins-Teisserenc H, de Latour RP, Mourah S, Bouaziz JD, Lebbé C, Bagot M, de Masson A

Abstract
Ifosfamide + etoposide (I+E) have been used to treat lymphomas, combined with platinum-based agents in Hodgkin disease or non-Hodgkin lymphomas including peripheral T-cell lymphomas. Monoclonal antibodies have induced long-term remissions in CTCL but are usually poorly effective in transformed disease. Allogeneic hematopoietic stem cell transplantation (alloHSCT) holds a potential for cure but relies on the existence of a pre-transplant CR which may require the use of chemotherapeutic regimens.

PMID: 32407544 [PubMed - as supplied by publisher]

Optimization of a Low-Cost, Sensitive PNA Clamping PCR Method for JAK2 V617F Variant Detection.

J Appl Lab Med. 2020 May 14;:

Authors: Di Francia R, Crisci S, Muto T, Giancola C, Petriccone L, Catapano O, Cummarro A, Pinto A, Frigeri F

Abstract
BACKGROUND: The JAK2 V617F variant is diagnostic for myeloproliferative neoplasms, a group of clonal disorders of hematopoietic stem and progenitor cells. Although several approaches have been developed to detect the variant, a gold standard diagnostic method has not yet been defined. We describe a simple, fast, and cost-effective PCR-based approach that enhances test specificity and sensitivity by blocking the amplification of the large excess of wild-type DNA.
METHODS: The method involves using an oligo peptide nucleic acid (PNA) perfectly matching its corresponding DNA sequence. The PCR protocol was optimized by collecting a detailed thermodynamic data set on PNA-DNA wild-type duplexes by circular dichroism melting experiments. The specificity and sensitivity of PNA clamping PCR were assessed by genotyping 50 patients with myeloproliferative neoplasm who carried the JAK2 V617F variant and 50 healthy donors.
RESULTS: The optimized protocol enabled selective amplification of the variant alleles, achieving maximum sensitivity (100%) and specificity (100%). Analytical sensitivity was 0.05% of variant alleles as assessed by serial dilutions of DNA from the HEL cell line (which carries the JAK2 V617F variant) mixed to wild-type DNA from healthy donors. The JAK2 V617F variant test performed according to this method has better diagnostic performance than its 2 main PCR-based competitors, at much lower cost.
CONCLUSIONS: High sensitivity and specificity and cost-effectiveness make PNA clamping PCR a useful testing platform for the detection of minor allele variants in small-scale diagnostic laboratories. It promises to improve patient care while enabling significant healthcare savings.

PMID: 32407536 [PubMed - as supplied by publisher]

Pharmacogenetic evaluation of metformin and sulphonylurea response in Mexican Mestizos with type 2 diabetes.

Curr Drug Metab. 2020 May 14;:

Authors: Marta M, Katy SP, Joel JS, Jazmin ME, Carolina RS, de Los Ángeles GM, Guadalupe OM

Abstract
BACKGROUND: In Mexico, approximately 25% of patients with type 2 diabetes (T2D) have adequate glycemic control. Polymorphisms in pharmacogenetic genes have been shown to have clinical consequences resulting in drug toxicity or therapeutic inefficacy.
OBJECTIVE: To evaluate the impact of variants in genes known to be involved in the response to oral hypoglycemic drugs, such as CYP2C9, OCT, MATE, ABCA1 and C11orf65, in the Mexican Mestizo population of T2D patients.
METHODS: In this study, 265 patients with T2D were enrolled from Hospital Juárez de México, Mexico City. Genotyping was performed by TaqMan® assays. SNP-SNP interactions were analyzed using the multifactor dimensionality reduction (MDR) method.
RESULTS: Carriers of the del allele of rs72552763 could achieve a better glycemic control than noncarriers. There was a significant difference in plasma glucose and HbA1c levels among rs622342 genotypes. The results suggested a SNP-SNP interaction between rs72552763 and rs622342 OCT1 and rs12943590 MATE2.
CONCLUSION: The interaction between rs72552763 and rs622342 in OCT1, and rs12943590 in MATE2 suggested an important role of these polymorphisms in metformin response in T2D Mexican Mestizo population.

PMID: 32407269 [PubMed - as supplied by publisher]

Targeting mitochondrial fusion and fission proteins for cardioprotection.

J Cell Mol Med. 2020 May 14;:

Authors: Hernandez-Resendiz S, Prunier F, Girao H, Dorn G, Hausenloy DJ, EU-CARDIOPROTECTION COST Action (CA16225)

Abstract
New treatments are needed to protect the myocardium against the detrimental effects of acute ischaemia/reperfusion (IR) injury following an acute myocardial infarction (AMI), in order to limit myocardial infarct (MI) size, preserve cardiac function and prevent the onset of heart failure (HF). Given the critical role of mitochondria in energy production for cardiac contractile function, prevention of mitochondrial dysfunction during acute myocardial IRI may provide novel cardioprotective strategies. In this regard, the mitochondrial fusion and fissions proteins, which regulate changes in mitochondrial morphology, are known to impact on mitochondrial quality control by modulating mitochondrial biogenesis, mitophagy and the mitochondrial unfolded protein response. In this article, we review how targeting these inter-related processes may provide novel treatment targets and new therapeutic strategies for reducing MI size, preventing the onset of HF following AMI.

PMID: 32406208 [PubMed - as supplied by publisher]

25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2.

Nutrients. 2020 May 09;12(5):

Authors: D'Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, Keller F, Cantù M

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.

PMID: 32397511 [PubMed - indexed for MEDLINE]

12 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 2020/05/14

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.

Epigenetic fragility of the endocannabinoid system under stress: risk for mood disorders and pharmacogenomic implications.

Epigenomics. 2020 May 12;:

Authors: Ferber SG, Roth TL, Weller A

PMID: 32396405 [PubMed - as supplied by publisher]

Identification and functional characterization of CYP4V2 genetic variants exhibiting decreased activity of lauric acid metabolism.

Ann Hum Genet. 2020 May 12;:

Authors: Jarrar YB, Shin JG, Lee SJ

Abstract
The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein-coding variants were studied, including three novel variants (L22V, R287T, and G410C) and three previously reported variants (R36S, Q259K, and H331P). The cDNA sequences encoding each amino acid variant and the wild-type CYP4V2 protein were cloned into the pcDNA/PDEST40 expression vector and transfected into eukaryotic 293T cells for overexpression of the CYP4V2 coding variants. CYP4V2 H331P and CYP4V2 G410C exhibited significant decreases in activity for lauric acid oxidation (20-30% of wild-type activity), when compared to the wildtype, which was correlated with low expression of CYP4V2 H331P and G410C substituted proteins. The other four CYP4V2 amino variants were comparable to wild-type CYP4V2 for lauric acid metabolism. The CYP4V2 H331P and G410C substitutions were predicted to cause a structural change through in silico analysis. In conclusion, the present study provides functional information about CYP4V2 genetic variants. These findings will be valuable for interpreting individual variations in phenotypes associated with CYP4V2 function in the clinical setting.

PMID: 32396266 [PubMed - as supplied by publisher]

Factors Associated with Declining to Participate in a Pediatric Oncology Next Generation Sequencing Study.

JCO Precis Oncol. 2020;4:202-211

Authors: Howard Sharp KM, Jurbergs N, Ouma A, Harrison L, Gerhardt E, Taylor L, Hamilton K, McGee RB, Nuccio R, Quinn E, Hines-Dowell S, Kesserwan C, Sunkara A, Gattuso JS, Pritchard M, Mandrell B, Relling MV, Haidar CE, Kang G, Johnson LM, Nichols KE

Abstract
Purpose: For the advances of pediatric oncology next generation sequencing (NGS) research to equitably benefit all children, a diverse and representative sample of participants is needed. However, little is known about demographic and clinical characteristics that differentiate families who decline enrollment in pediatric oncology NGS research.
Methods: Demographic and clinical data were retrospectively extracted for 363 pediatric oncology patients (0-21 years) approached for enrollment on Genomes for Kids (G4K), a study examining the feasibility of comprehensive clinical genomic analysis of tumors and paired normal samples. Demographic and clinical factors that significantly differentiated which families declined were subsequently compared to enrollment in Clinical Implementation of Pharmacogenetics (PG4KDS) for 348 families, a pharmacogenomics study with more explicit therapeutic benefit examining genes affecting drug responses and metabolism.
Results: Fifty-three (14.6%) families declined enrollment in G4K. Race/ethnicity was the only variable that significantly differentiated study refusal using multivariate logistic regression, with families of black children more likely to decline enrollment compared to families of non-Hispanic or Hispanic white children. Reasons for declining G4K were generally consistent with other pediatric genomics research, with feeling overwhelmed and insurance discrimination fears most frequently cited. Families of black children were also more likely to decline enrollment in PG4KDS. Thirteen (3.7%) of the 348 families approached for both studies declined PG4KDS.
Conclusion: Race/ethnicity differentiated study declination across two different pediatric oncology genomics studies, suggesting enrollment disparities in the context of pediatric oncology genomics research. Genomics research participant samples that do not fully represent racial and ethnic minorities risk further exacerbating health disparities. Additional work is needed to understand the nuances of parental decision making in genomic research and facilitate enrollment of diverse patient populations.

PMID: 32395682 [PubMed]

TRIB3 rs6037475 is a potential biomarker for predicting felodipine drug response in Chinese patients with hypertension.

Ann Transl Med. 2020 Apr;8(7):437

Authors: He F, Sun B, Li L, Liu M, Lin W, Liu L, Sun Y, Luo Y, Wu L, Lu L, Zhang W, Zhou Z

Abstract
Background: Our previous studies have found that single nucleotide polymorphisms (SNPs) of tribbles homolog 3 (TRIB3) are related to the hypotensive effects of calcium-channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors. In this study, we aimed at exploring and validating the effect of TRIB3 polymorphism on antihypertensive drugs responses.
Methods: A total of 830 hypertensive patients, who were administered with open-labeled hydrochlorothiazide (12.5 mg once daily) and randomly assigned to off-labeled felodipine (5 mg) or a matched placebo combination treatment (1:1), were selected from the Felodipine Event Reduction (FEVER) study. A strategy of screening 259 samples and validating the remaining 531 samples was implemented. Four functional SNPs were selected (rs2295490, rs11470129, rs4815567 and rs6037475 in TRIB3). A mixed linear model was performed to analyze the effects of TRIB3 SNPs on antihypertensive drugs responses.
Results: We found that TRIB3 rs6037475 CC genotype was associated with a reduction of diastolic blood pressure (DBP) (P=6.3×10-3) in the felodipine treatment group of screening set, and was also associated with a reduction of systolic blood pressure (SBP) (P=0.021), DBP (P=6.0×10-3) and mean arterial pressure (MAP) (P=0.021) in the felodipine treatment group of the validation set. As for the reductions influenced by the rs2295490, rs11470129 and rs4815567 genetic variations, however, the adjusted P-value did not reach statistical significance. Combined screening and validation set analysis found that patients with TRIB3 rs6037475 CC genotype had a significant higher mean SBP, DBP and MAP than those with TT genotype in the felodipine treatment group (CC vs. TT -10.2±0.74 vs. -17.8±0.21, P=7.8×10-3; -4.6±0.50 vs. -10.2±0.23, P=3.0×10-4; -6.5±0.54 vs. -12.7±0.14, P=3.0×10-4, respectively).
Conclusions: These results suggest that TRIB3 rs6037475 genetic variation can be useful as a bio-marker for predicting felodipine drug response in Chinese patients with hypertension.

PMID: 32395481 [PubMed]

Schizophrenia-associated gene dysbindin-1 and tardive dyskinesia.

Drug Dev Res. 2020 May 11;:

Authors: Maes MS, Lu JY, Tiwari AK, Freeman N, de Luca V, Müller DJ, Voineskos AN, Potkin SG, Lieberman JA, Meltzer HY, Remington G, Kennedy JL, Zai CC

Abstract
Tardive dyskinesia (TD) is a potentially irreversible movement disorder observed following long-term antipsychotic exposure. Its cause is unknown; however, a genetic component has been supported by studies of affected families. Dysbindin-1, encoded by the dystrobrevin-binding protein 1 DTNBP1 gene, has been associated with schizophrenia and is potentially involved in dopamine neurotransmission through its regulation of dopamine release and dopamine D2 receptor recycling, making it a candidate for investigation in TD. We investigated common variants across the DTNBP1 gene in our schizophrenia/patients with schizoaffective disorder of European ancestry. We found a number of DTNBP1 three-marker haplotypes to be associated with TD occurrence and TD severity (p < 0.05). These preliminary findings, if replicated in larger independent samples, would suggest that drugs targeting dysbindin-1 may be an option in the prevention and treatment of TD.

PMID: 32394511 [PubMed - as supplied by publisher]