CYP Genotypes Are Associated with Toxicity and Survival in Osteosarcoma Patients.

J Adolesc Young Adult Oncol. 2020 Apr 16;:

Authors: Trujillo-Paolillo A, Salinas-Souza C, Dias-Oliveira I, Petrilli AS, Toledo SRC

Abstract
Purpose: Osteosarcoma is the malignant bone tumor most common in children and adolescents. Many cytochrome P-450 (CYP) members detoxify anticancer drugs used in osteosarcoma treatment, and thus, the aim of the present study was to investigate CYP polymorphisms in osteosarcoma patients. Materials and Methods: The present study investigated DNA from peripheral blood from 70 osteosarcoma patients treated with high doses of cisplatin, doxorubicin, and methotrexate. CYP1A2*1F (163C>A; rs762551); CYP2C9*3 (1075A>C; rs1057910); and CYP3A5*3 (6986A>G; rs776746) polymorphisms were investigated through real-time PCR using TaqMan probes. Results: The CYP2C9*3 allele did not present any association with clinical events. The CYP1A2 CC/AC genotypes were associated with ototoxicity occurrence (p = 0.041, odds ratio [OR] = 8.4) and high grades of ototoxicity (p = 0.039, OR = 10.7), when compared with patients carrying the CYP1A2 AA genotype. The CYP1A2 CC genotype was associated with high grades of diarrhea (p = 0.043, OR = 4.6) and fever (p = 0.041, OR = 7.1) in comparison with the CYP1A2 AA/AC genotypes. The CYP3A5 CC genotype was associated with weight loss (p = 0.009, OR = 3.8) and high grades of hepatotoxicity (p = 0.010, OR = 4.3) when compared with the CYP3A5 TT/CT genotypes. The CYP3A5 CC/CT genotypes were associated with high grades of vomit (p = 0.013, OR = 10.8), pulmonary relapse absence (p = 0.029, OR = 9.5), and better overall and event-free survivals (p = 0.017, hazard ratio [HR] = 3.1; p = 0.044, HR = 2.5; respectively) when compared with the CYP3A5 AA genotype. Conclusion: CYP1A2*1A and CYP3A5*3 alleles were associated with toxicity events. CYP3A5*3 allele was associated with better survival. Thus, CYP genotypes might be promising markers to tailoring treatment in osteosarcoma patients.

PMID: 32298597 [PubMed - as supplied by publisher]

Predictors of response to medications for asthma in pediatric patients: A systematic review of the literature.

Pediatr Pulmonol. 2020 Apr 16;:

Authors: Rodriguez-Martinez CE, Sossa-Briceño MP, Castro-Rodriguez JA

Abstract
OBJECTIVES: There has been no systematic review of studies aimed to predict differential responses to medication regimens for asthma controller therapies in pediatric patients. The aim of the present study was to summarize those identifying biomarkers for the different asthma controller therapies.
METHODS: Studies published by June 2019 that report phenotypic or genotypic characteristics or biomarkers that could potentially serve as response predictors to asthma controller therapies in pediatric patients were included. The quality of studies was assessed using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale tool.
RESULTS: Of 385 trials identified, 30 studies were included. Children with asthma and a positive family history of asthma, with more severe disease, of the white race, with allergy biomarkers, nonobese, with lower lung function, high bronchial hyperresponsiveness to methacholine, or having variants in the FCER2 and CRHR1 gene respond better to inhaled corticosteroids (ICS). Younger age (<10 years), short disease duration (<4 years), high cotinine and urinary leukotriene E4 (LTE4) levels, and 5/5 ALOX5 were associated with a better response to leukotriene receptor antagonist (LTRA). For patients that remain symptomatic, white Hispanics were more likely to respond to LTRA, blacks to ICS, white non-Hispanics to LTRA or LABA, and children without a history of eczema, regardless of race or ethnicity to LABA set-up therapy. In severe persistent asthma, those with atopy and body mass index greater than or equal 25 were more likely to benefit from omalizumab.
CONCLUSION: Several phenotypic characteristics, biomarkers, or pharmacogenomics markers could be useful for predicting the best drug for asthma treatment.

PMID: 32297708 [PubMed - as supplied by publisher]

Pharmacogenetic study of ACE, AGT, CYP11B1, CYP11B2 and eNOS gene variants in hypertensive patients from Faisalabad, Pakistan.

J Pak Med Assoc. 2020 Apr;70(4):624-629

Authors: Hussain M, Bilal A, Awan FR

Abstract
OBJECTIVE: To investigate the association of genetic variants of renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes, and the drug efficacy of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker.
METHODS: This two time-point study was conducted from April to November 2016 at Allied Hospital, Faisalabad and National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, and comprised of hypertensive patients taking angiotensin-converting enzyme inhibitor and angiotensin receptor blocker who were followed up for 12 weeks. Baseline and follow-up clinical and biochemical parameters were measured for all patients. Total 11 polymorphisms were genotyped by polymerase chain reaction, polymerase chain reaction-restriction fragment length polymorphism and amplification-refractory mutation system-polymerase chain reaction assays. Data was divided into baseline and follow-up groups, while the latter group was further divided into responding and non-responding subgroups on the basis of patient response to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker drugs. Data was analysed using SPSS 20.
RESULTS: Of the 45 patients, 25(55.5%) were females and 20(44.5%) were males. There was a significant reduction in the systolic blood pressure (p=0.004) and low-density lipoprotein cholesterol (p<0.001) from the baseline to the follow-up. Systolic blood pressure was significantly reduced in the responding group (p=0.003), while diastolic blood pressure (p=0.121) was not significantly different. There was no effect of angiotensin-converting enzyme, angiotensinogen, 11-beta-hydroxylase, aldosterone synthase and endothelial nitric oxide synthase gene polymorphisms on angiotensin converting enzyme inhibitor and angiotensin receptor blocker efficacy.
CONCLUSIONS: Inter-individual response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker was found to be independent of genetic polymorphisms in renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes.

PMID: 32296206 [PubMed - in process]

Development of efficient on-bead protein elution process coupled to ultra-high performance liquid chromatography-tandem mass spectrometry to determine immunoglobulin G subclass and glycosylation for discovery of bio-signatures in pancreatic disease.

J Chromatogr A. 2020 Mar 14;:461039

Authors: Shiao JY, Chang YT, Chang MC, Chen MX, Liu LW, Wang XY, Tsai YJ, Kuo TC, Tsai IL

Abstract
Type 1 autoimmune pancreatitis (AIP) is a kind of IgG4-related disease in which higher IgG4 and total IgG levels have been found in patient serum. Due to the similar imaging features and laboratory parameters between AIP and pancreatic ductal adenocarcinoma (PDAC), a differential diagnosis is still challenging. Since IgG profiles can be potential bio-signatures for disease, we developed and validated a method which coupled on-bead enzymatic protein elution process to an efficient UHPLC-MS/MS method to determine IgG subclass and glycosylation. A stable-isotope labeled IgG was incorporated as internal standard to achieve accurate quantification. For calibration curves, the correlation coefficients for total IgG and the four IgG subclasses were higher than 0.995. Intraday (n = 5) and interday (n = 3) precisions of the peak area ratios of LLOQ, low, medium, and high QC samples were all less than 6.6% relative standard deviation (% RSD), and the accuracies were between 93.5 and 114.9%. Calibration curves, precision, and accuracy were also evaluated for 26 IgG glycopeptides. The method was applied to samples from healthy controls and patients with AIP and PDAC. Distinct IgG patterns were discovered among the groups, and 7 glycopeptides showed high potential in differentiating AIP and PDAC. The results demonstrated that the developed method is suitable for multi-feature analysis of human IgG, and the discovered IgG profiles can be used as bio-signatures for AIP and PDAC.

PMID: 32295703 [PubMed - as supplied by publisher]

Human Liver Spheroids as a Model to Study Aetiology and Treatment of Hepatic Fibrosis.

Cells. 2020 Apr 14;9(4):

Authors: Hurrell T, Kastrinou-Lampou V, Fardellas A, Hendriks DFG, Nordling Å, Johansson I, Baze A, Parmentier C, Richert L, Ingelman-Sundberg M

Abstract
Non-alcoholic fatty liver disease affects approximately one billion adults worldwide. Non-alcoholic steatohepatitis (NASH) is a progressive disease and underlies the advancement to liver fibrosis, cirrhosis, and hepatocellular carcinoma, for which there are no FDA-approved drug therapies. We developed a hetero-cellular spheroid system comprised of primary human hepatocytes (PHH) co-cultured with crude fractions of primary human liver non-parenchymal cells (NPC) from several matched or non-matched donors, to identify phenotypes with utility in investigating NASH pathogenesis and drug screening. Co-culture spheroids displayed stable expression of hepatocyte markers (albumin, CYP3A4) with the integration of stellate (vimentin, PDGFRβ), endothelial (vWF, PECAM1), and CD68-positive cells. Several co-culture spheroids developed a fibrotic phenotype either spontaneously, primarily observed in PNPLA3 mutant donors, or after challenge with free fatty acids (FFA), as determined by COL1A1 and αSMA expression. This phenotype, as well as TGFβ1 expression, was attenuated with an ALK5 inhibitor. Furthermore, CYP2E1, which has a strong pro-oxidant effect, was induced by NPCs and FFA. This system was used to evaluate the effects of anti-NASH drug candidates, which inhibited fibrillary deposition following 7 days of exposure. In conclusion, we suggest that this system is suitable for the evaluation of NASH pathogenesis and screening of anti-NASH drug candidates.

PMID: 32295224 [PubMed - in process]

MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients.

Int J Mol Sci. 2020 Apr 14;21(8):

Authors: Olivera GG, Yáñez Y, Gargallo P, Sendra L, Aliño SF, Segura V, Sanz MÁ, Cañete A, Castel V, Font De Mora J, Hervás D, Berlanga P, Herrero MJ

Abstract
Single nucleotide polymorphisms (SNPs) in Pharmacogenetics can play an important role in the outcomes of the chemotherapy treatment in Neuroblastoma, helping doctors maximize efficacy and minimize toxicity. Employing AgenaBioscience MassArray, 96 SNPs were genotyped in 95 patients looking for associations of SNP with response to induction therapy (RIT) and grade 3-4 toxicities, in High Risk patients. Associations of SNPs with overall (OS) and event-free (EFS) survival in the whole cohort were also explored. Cox and logistic regression models with Elastic net penalty were employed. Association with grade 3-4 gastrointestinal and infectious toxicities was found for 8 different SNPs. Better RIT was correlated with rs726501 AG, rs3740066 GG, rs2010963 GG and rs1143684 TT (OR = 2.87, 1.79, 1.23, 1.14, respectively). EFS was affected by rs2032582, rs4880, rs3814058, rs45511401, rs1544410 and rs6539870. OS was influenced by rs 1801133, rs7186128 and rs1544410. Remarkably, rs1801133 in MTHFR (p = 0.02) and rs1544410 in VDR (p = 0.006) also added an important predictive value for OS to the MYCN status, with a more accurate substratification of the patients. Although validation studies in independent cohorts will be required, the data obtained supports the utility of Pharmacogenetics for predicting Neuroblastoma treatment outcomes.

PMID: 32295184 [PubMed - in process]

Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes.

Bosn J Basic Med Sci. 2019 Nov 08;19(4):368-374

Authors: Dujic T, Bego T, Malenica M, Velija-Asimi Z, Ahlqvist E, Groop L, Pearson ER, Causevic A, Semiz S

Abstract
The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.

PMID: 31070566 [PubMed - indexed for MEDLINE]

Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients.

Am J Transplant. 2019 01;19(1):238-246

Authors: Quteineh L, Wójtowicz A, Bochud PY, Crettol S, Vandenberghe F, Venetz JP, Manuel O, Golshayan D, Lehmann R, Mueller NJ, Binet I, van Delden C, Steiger J, Mohacsi P, Dufour JF, Soccal PM, Kutalik Z, Marques-Vidal P, Vollenweider P, Recher M, Hess C, Pascual M, Eap CB, Swiss Transplant Cohort Study

Abstract
New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n1  = 696). Positive results were tested in a first STCS replication sample (n2  = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n3  = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect.

PMID: 29920932 [PubMed - indexed for MEDLINE]

13 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 2020/04/16

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.

13 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 2020/04/16

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.

Identification of host variants associated with overall survival of esophageal cancer patients receiving platinum-based therapy.

Pharmacogenomics. 2020 Apr 14;:

Authors: Rumiato E, Boldrin E, Malacrida S, Battaglia G, Sileni VC, Ruol A, Amadori A, Saggioro D

Abstract
Aim: Clinical features of esophageal cancer (EC) patients have poor prognostic power. Thus, it is paramount to discover biomarkers that can allow a more accurate survival prediction. Methods: To detect genetic variants associated with survival, DNA from 120 patients treated with cisplatin-based neoadjuvant therapy were genotyped using drug metabolism enzymes and transporters array. Results: We identified two variants: the rs2038067 in PPARD (p = 0.0004) and the rs683369 (F160L) in SLC22A1 (p = 0.001). Their prognostic power was greater than that of clinical stage alone (p = 0.017) and comparable to that of response to neoadjuvant therapy (p = 0.71). Interestingly, the prognostic accuracy of response models increased significantly when genetic variables were included (p = 0.003). Conclusion: Our data, though preliminary, strengthen the potential utility of germline variants for a better-tailored management of EC patients.

PMID: 32285752 [PubMed - as supplied by publisher]

Liquid biopsy for the detection of clinical biomarkers in early breast cancer: new insights and challenges.

Pharmacogenomics. 2020 Apr 14;:

Authors: Matsutani A, Udagawa C, Matsunaga Y, Nakamura S, Zembutsu H

Abstract
The widespread use of breast screening programs has contributed to the detection of early stage breast cancer, which is often asymptomatic. Early diagnosis is essential to avoid overtreatment and improve clinical outcomes, as early stage breast cancer is rarely life-threatening if detected quickly. Despite this, tissue biopsy remains the principle method for detecting these cancers. Liquid biopsy has been recently proposed as a promising detection method in oncology that is not only less invasive but also contributes to the early diagnosis of breast cancer. Here, we describe the clinical utility of liquid biopsy as a tool for the early detection of breast cancer.

PMID: 32284011 [PubMed - as supplied by publisher]

Nimodipine-induced junctional bradycardia in an elderly patient with subarachnoid hemorrhage.

Pharmacogenomics. 2020 Apr 14;:

Authors: James CL, Turnbull MT, Freeman WD

Abstract
Subarachnoid hemorrhage is a devastating form of stroke with often detrimental outcomes for patients. Here we describe a patient with subarachnoid hemorrhage treated with nimodipine, which resulted in marked bradycardia with junctional atrioventricular heart block. Nimodipine is metabolized predominantly by the cytochrome P450 3A subfamily, and its use is often associated with adverse events, such as hypotension and bradycardia, which can be exacerbated by advanced age. Our patient had the CYP3A5*3/*3 genotype, possibly predisposing her to poor metabolism of this drug. Our case report demonstrates the potential for pharmacogenomics in patients with subarachnoid hemorrhage to help predict their response to nimodipine, minimize adverse drug reactions, and potentially individualize dosing to improve future clinical outcomes.

PMID: 32284009 [PubMed - as supplied by publisher]

Vitamin B12 Status and Optimal Range for Hemoglobin Formation in Elite Athletes.

Nutrients. 2020 Apr 09;12(4):

Authors: Krzywański J, Mikulski T, Pokrywka A, Młyńczak M, Krysztofiak H, Frączek B, Ziemba A

Abstract
BACKGROUND: Athletes and coaches believe in the ergogenic effect of vitamin B12 (which results from enhanced erythropoiesis) and they often insist on its unjustified supplementation. Therefore, our study aimed to assess the vitamin B12 status in Polish elite athletes and its influence on red blood cell parameters.
METHODS: In total, 1131 blood samples were collected during six years from 243 track and field athletes divided into strength and endurance groups, as well as according to the declared use of vitamin B12 injections.
RESULTS: An average vitamin B12 concentration in all subjects was 739 ± 13 pg/mL, with no cases of deficiency. A weak but significant relationship was found between vitamin B12 and hemoglobin concentrations. A significant increase in hemoglobin appeared from very low vitamin B12 concentration and up to approx. 400 pg/mL, while hemoglobin did not significantly change from 700 pg/mL and onwards. Vitamin B12 injections were used by 34% of athletes, significantly more often by endurance than by strength athletes. In athletes who declared no use of injections, a higher concentration of vitamin B12 was observed in the endurance group.
CONCLUSION: The main finding of the present study is the determination of the range of vitamin B12 concentration which may favor better hemoglobin synthesis in athletes. They should regularly monitor vitamin B12 concentration and maintain the range of 400-700 pg/mL as it may improve red blood cell parameters. We might suggest application of a supplementation if necessary. Special attention is required in athletes with a vitamin B12 concentration below 400 pg/mL.

PMID: 32283824 [PubMed - in process]

17 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 2020/04/14

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.

GABAergic neurons in the insular cortex play an important role in cue-morphine reward memory reconsolidation.

Life Sci. 2020 Apr 08;:117655

Authors: Sun K, Xiao L, Wu Y, Zuo D, Zhang C, Liu S, He Z, Rong S, Wang F, Sun T

Abstract
AIMS: There have been recent reports that reconsolidation-based interventions attenuate drug reward memories in rodents. The insular cortex (IC) is an essential part of neural circuits that underlie cue-drug memory reconsolidation. GABAergic interneurons in the IC are a potent control on network excitability and play an important role in the inhibitory mediation of reward circuits. However, the function of GABAergic neurons in the IC for memory reconsolidation remains unclear; therefore, we conducted this study to clarify this.
MAIN METHODS: We applied morphine-induced conditioned place preference (mCPP) paradigm and pharmacogenetic techniques to study the mediation effect of GABAergic neurons in the IC on mCPP reconsolidation. Moreover, we preliminarily explored the possible mechanisms of mediating GABAergic neurons in the IC involved in mCPP reconsolidation by assessing Arc and Erg-1 protein levels in the IC.
KEY FINDINGS: We found that post-retrieval immediate activation of GABAergic neurons in the IC impaired mCPP reconsolidation. In addition, this effect was not reversed by a priming morphine injection. Further, post-retrieval inhibition and non-retrieval excitation of GABAergic neurons in the IC had no effect on mCPP.
SIGNIFICANCE: Taken together, our findings suggest that GABAergic neurons in the IC are closely involved in mCPP reconsolidation. Specifically, their excitation could eliminate established mCPP and prevent the relapse risk by disruption of the reconsolidation. The underlying molecular biological mechanisms could involve reduced Arc and Erg-1 levels.

PMID: 32277980 [PubMed - as supplied by publisher]

The impact of ABCB1 gene polymorphism and its expression on non-small-cell lung cancer development, progression and therapy - preliminary report.

Sci Rep. 2020 Apr 10;10(1):6188

Authors: Zawadzka I, Jeleń A, Pietrzak J, Żebrowska-Nawrocka M, Michalska K, Szmajda-Krygier D, Mirowski M, Łochowski M, Kozak J, Balcerczak E

Abstract
The ABCB1 gene belongs to ATP binding cassette (ABC) transporter genes that has been previously implicated in cancer progression and drug response. This study aimed to evaluate the association between the SNP 3435 and the expression of the ABCB1 gene in lung cancer patients in the Polish population in comparison to clinicopathological parameters and treatment. 150 RNA and 47 DNA samples were isolated from 49 lung cancer cases including both tissue samples and blood taken from the same patients at three time points: diagnosis, 100 days and one year after the surgical intervention. Qualitative and real-time PCR analysis of expression were done, also genotyping by PCR-RFLP. Mutant homozygous TT and allele T are present statistically significantly more frequently in the group of patients with lung cancer. There is no difference with expression level in lung cancer tissue and blood sample taken from the same patients before surgical treatment. On the basis of blood samples analysis it was observed that the expression level of ABCB1 mRNA was growing in time. Higher levels were marked after 100 days and one year after the surgical intervention. The complementary pharmacological treatment induced higher expression levels of ABCB1. The presented data suggest an important role of ABCB1 in lung cancer, the increasing level of ABCB1 mRNA which can be connected with induction of multidrug resistance mechanism is also significant, that observation must be confirmed in further analysis.

PMID: 32277145 [PubMed - as supplied by publisher]

Survey of physicians' views on the clinical implementation of pharmacogenomics-based personalized therapy.

Transl Clin Pharmacol. 2020 Mar;28(1):34-42

Authors: Kim WY, Kim HS, Oh M, Shin JG

Abstract
Despite quantitative increases and qualitative advances in pharmacogenomics (PGx) research, the clinical implementation of PGx-based personalized therapy has still been limited. The objective of this study was to assess physicians' self-reported knowledge of PGx-based personalized therapy, and to explore the most problematic and highest priority barriers preventing physicians from applying PGx into clinical practice under the Korean healthcare system. A 36-question survey was distributed to 53 physicians with various specialties in Korea. In the physicians' self-perceived knowledge, twenty-eight physicians (53%) reported a lack sufficient knowledge about PGx. The perceived largest barrier to clinical implementation of PGx was the high cost of PGx testing, followed by a lack of PGx education for healthcare providers or lack of clinical PGx experts. Physicians without clinical PGx experience or with indirect experience reported that the largest barrier to clinical implementation of PGx was the high cost of PGx testing, while physicians with clinical PGx experience pointed out that a lack of patients' education was the major concern, followed by a lack of PGx education for healthcare providers or lack of clinical PGx experts. The highest priority problem was reported to be a lack of actionable guidelines for drug selection and dosing using PGx. In conclusion, we should increase and expand extensive educational programs for healthcare providers and patients, and to develop and establish a clinical decision support systems for PGx-based personalized therapy in Korea.

PMID: 32274379 [PubMed]

SLC30A8, CDKAL1, TCF7L2, KCNQ1 and IGF2BP2 are Associated with Type 2 Diabetes Mellitus in Iranian Patients.

Diabetes Metab Syndr Obes. 2020;13:897-906

Authors: Vatankhah Yazdi K, Kalantar SM, Houshmand M, Rahmanian M, Manaviat MR, Jahani MR, Kamalidehghan B, Almasi-Hashiani A

Abstract
Background: Type 2 diabetes mellitus (T2DM) is a serious public health issue with significantly increasing rates across the world. The genome-wide association studies (GWAS) have previously manifested involved genes that remarkably enhance the risk of T2DM. In this study, the association of common variants with T2DM risk has been identified among Iranian population from Tehran province of Iran.
Methods: Here, the association of refSNPs with T2DM risk was examined on peripheral blood samples of 268 individuals including control group and patients with T2DM using the tetra amplification refractory mutation system (ARMS) methods and direct genomic DNA sequencing.
Results: Our study demonstrated that SLC30A8 rs13266634 (T/C), CDKAL1 rs10946398 (A/C), TCF7L2 rs7903146 (C/T), KCNQ1 rs2237892 (T/C), and IGF2BP2 rs1470579 (A/C) polymorphisms are significantly associated with type 2 diabetes, but no significant association was identified for FTO rs8050136 and MTNR1B rs10830963 polymorphisms.
Conclusion: The prediction of refSNPs is remarkably needed for pharmacogenetics and pharmacogenomic approaches, in which the information would be useful for clinicians to optimize therapeutic strategies and adverse drug reactions in patients with T2DM.

PMID: 32273741 [PubMed]

The Relationship Between Selected CNR1, MC4R, LEP, FTO and VDR Gene Polymorphisms and Several Basic Toxicological Parameters Among Persons Occupationally Exposed to Arsenic, Cadmium and Lead.

J Clin Med. 2020 Apr 07;9(4):

Authors: Matys T, Szymańska-Chabowska A, Bogunia-Kubik K, Smyk B, Kamińska M, Mazur G, Poręba R, Gać P

Abstract
The purpose of this work was to assess the influence of selected CNR1, MC4R, LEP, FTO and VDR FOKI gene polymorphisms on blood and urine concentration markers of lead, cadmium and arsenic in a population directly exposed to these metals. Eighty-five people exposed to lead, arsenic and cadmium were qualified to take part in the study. Standard urine samples and 25mL of venous blood from each worker were collected to assay basic laboratory and toxicological markers as well as selected single nucleotide polymorphisms (SNPs) within CNR1-cannabinoid receptor 1 gene (rs806368, rs806381, rs1049353, rs12720071), MC4R-melanocortin 4 receptor gene (rs17782313), LEP-leptin promoter gene (rs7799039), FTO-alpha-ketoglutarate-dependent dioxygenase gene (rs9939609) and VDR-vitamin D receptor (rs10735810) genes. It appeared that, except for the MC4R SNP, all the other polymorphisms were found to be associated with various laboratory parameters. Arsenic concentration in urine was associated with all four CNR1 and LEP SNPs, while cadmium concentration in blood was affected by the VDR polymorphism. Moreover, some significant relationships were also observed between CNR1 rs1049353 and FTO rs9939609 gene variants and markers of lead exposure. These results imply SNPs within genes coding for proteins involved in development of metabolic syndrome may be of prognostic value for persons directly exposed to lead, cadmium and arsenic.

PMID: 32272684 [PubMed]