Adverse Effects Associated With Newer Diabetes Therapies.

J Pharm Pract. 2017 Apr;30(2):238-244

Authors: Akiyode OF, Adesoye AA

Abstract
The increasing number of newer type 2 diabetes therapies has allowed providers an increased armamentarium for the optimal management of patients with diabetes. In fact, these newer agents have unique benefits in the management of type 2 diabetes. However, they are also associated with certain adverse effects. This review article aims to describe the notable adverse effects of these newer antidiabetic therapies including the glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter 2 inhibitors. The adverse effects reviewed herein include pancreatitis, medullary thyroid carcinoma, heart failure, gastrointestinal disturbances, renal impairment, and genitourinary infections. More clinical data are necessary to solidify the association of some of these adverse effects with the newer diabetes agents. However, it is important for health care practitioners to be well informed and prepared to properly monitor patients for these adverse effects.

PMID: 26169212 [PubMed - indexed for MEDLINE]

14 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 2017/07/08

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.

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

"systems biology"

These pubmed results were generated on 2017/07/08

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.

Sequential construction of a model for modular gene expression control, applied to spatial patterning of the Drosophila gene hunchback.

J Bioinform Comput Biol. 2016 04;14(2):1641005

Authors: Spirov AV, Myasnikova EM, Holloway DM

Abstract
Gene network simulations are increasingly used to quantify mutual gene regulation in biological tissues. These are generally based on linear interactions between single-entity regulatory and target genes. Biological genes, by contrast, commonly have multiple, partially independent, cis-regulatory modules (CRMs) for regulator binding, and can produce variant transcription and translation products. We present a modeling framework to address some of the gene regulatory dynamics implied by this biological complexity. Spatial patterning of the hunchback (hb) gene in Drosophila development involves control by three CRMs producing two distinct mRNA transcripts. We use this example to develop a differential equations model for transcription which takes into account the cis-regulatory architecture of the gene. Potential regulatory interactions are screened by a genetic algorithms (GAs) approach and compared to biological expression data.

PMID: 27122317 [PubMed - indexed for MEDLINE]

More Treatments on Deck for Alcohol Use Disorder.

JAMA. 2017 Jun 13;317(22):2267-2269

Authors: Lyon J

PMID: 28538998 [PubMed - indexed for MEDLINE]

Semantic Web, Reusable Learning Objects, Personal Learning Networks in Health: Key Pieces for Digital Health Literacy.

Stud Health Technol Inform. 2017;238:219-222

Authors: Konstantinidis ST, Wharrad H, Windle R, Bamidis PD

Abstract
The knowledge existing in the World Wide Web is exponentially expanding, while continuous advancements in health sciences contribute to the creation of new knowledge. There are a lot of efforts trying to identify how the social connectivity can endorse patients' empowerment, while other studies look at the identification and the quality of online materials. However, emphasis has not been put on the big picture of connecting the existing resources with the patients "new habits" of learning through their own Personal Learning Networks. In this paper we propose a framework for empowering patients' digital health literacy adjusted to patients' currents needs by utilizing the contemporary way of learning through Personal Learning Networks, existing high quality learning resources and semantics technologies for interconnecting knowledge pieces. The framework based on the concept of knowledge maps for health as defined in this paper. Health Digital Literacy needs definitely further enhancement and the use of the proposed concept might lead to useful tools which enable use of understandable health trusted resources tailored to each person needs.

PMID: 28679928 [PubMed - in process]

Issues Associated With the Use of Semantic Web Technology in Knowledge Acquisition for Clinical Decision Support Systems: Systematic Review of the Literature.

JMIR Med Inform. 2017 Jul 05;5(3):e18

Authors: Zolhavarieh S, Parry D, Bai Q

Abstract
BACKGROUND: Knowledge-based clinical decision support system (KB-CDSS) can be used to help practitioners make diagnostic decisions. KB-CDSS may use clinical knowledge obtained from a wide variety of sources to make decisions. However, knowledge acquisition is one of the well-known bottlenecks in KB-CDSSs, partly because of the enormous growth in health-related knowledge available and the difficulty in assessing the quality of this knowledge as well as identifying the "best" knowledge to use. This bottleneck not only means that lower-quality knowledge is being used, but also that KB-CDSSs are difficult to develop for areas where expert knowledge may be limited or unavailable. Recent methods have been developed by utilizing Semantic Web (SW) technologies in order to automatically discover relevant knowledge from knowledge sources.
OBJECTIVE: The two main objectives of this study were to (1) identify and categorize knowledge acquisition issues that have been addressed through using SW technologies and (2) highlight the role of SW for acquiring knowledge used in the KB-CDSS.
METHODS: We conducted a systematic review of the recent work related to knowledge acquisition MeM for clinical decision support systems published in scientific journals. In this regard, we used the keyword search technique to extract relevant papers.
RESULTS: The retrieved papers were categorized based on two main issues: (1) format and data heterogeneity and (2) lack of semantic analysis. Most existing approaches will be discussed under these categories. A total of 27 papers were reviewed in this study.
CONCLUSIONS: The potential for using SW technology in KB-CDSS has only been considered to a minor extent so far despite its promise. This review identifies some questions and issues regarding use of SW technology for extracting relevant knowledge for a KB-CDSS.

PMID: 28679487 [PubMed - in process]

Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models.

Br J Cancer. 2017 Jul 06;:

Authors: Belgiovine C, Bello E, Liguori M, Craparotta I, Mannarino L, Paracchini L, Beltrame L, Marchini S, Galmarini CM, Mantovani A, Frapolli R, Allavena P, D'Incalci M

Abstract
BACKGROUND: Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells.
METHODS: In this study we investigated whether lurbinectedin has the ability to modulate the inflammatory microenvironment and the viability of myeloid cells in tumour-bearing mice.
RESULTS: Administration of lurbinectedin significantly and selectively decreased the number of circulating monocytes and, in tumour tissues, that of macrophages and vessels. Similar findings were observed when a lurbinectedin-resistant tumour variant was used, indicating a direct effect of lurbinectedin on the tumour microenviroment. In vitro, lurbinectedin induced caspase-8-dependent apoptosis of human purified monocytes, whereas at low doses it significantly inhibited the production of inflammatory/growth factors (CCL2, CXCL8 and VEGF) and dramatically impaired monocyte adhesion and migration ability. These findings were supported by the strong inhibition of genes of the Rho-GTPase family in lurbinectedin-treated monocytes.
CONCLUSIONS: The results illustrate that lurbinectedin affects at multiple levels the inflammatory microenvironment by acting on the viability and functional activity of mononuclear phagocytes. These peculiar effects, combined with its intrinsic activity against cancer cells, make lurbinectedin a compound of particular interest in oncology.British Journal of Cancer advance online publication, 6 July 2017; doi:10.1038/bjc.2017.205 www.bjcancer.com.

PMID: 28683469 [PubMed - as supplied by publisher]

Florida Best Practice Psychotherapeutic Medication Guidelines for Adults With Major Depressive Disorder.

J Clin Psychiatry. 2017 Jun;78(6):703-713

Authors: McIntyre RS, Suppes T, Tandon R, Ostacher M

Abstract
OBJECTIVE: Herein we provide the 2015 update for the Florida Best Practice Psychotherapeutic Medication Guidelines (FPG) for major depressive disorder (MDD). The FPG represent evidence-based decision support for practitioners providing care to adults with MDD.
PARTICIPANTS: The consensus meeting included representatives from the Florida Agency for Health Care Administration (FAHCA), advocacy members, academic experts in MDD, and multidisciplinary mental health clinicians, as well as health policy experts. The FAHCA provided funding support for the FPG.
EVIDENCE: Evidence was limited to results from adequately powered, randomized, double-blind, placebo-controlled trials; in addition, pooled-, meta-, and network-analyses were included. Recommendations were based on consensus arrived at by the multistakeholder Florida Expert Panel. Articles selected were identified on the electronic search engine PubMed with the dates 2010 to present. The search terms were major depressive disorder, psychopharmacology, antidepressants, psychotherapy, neuromodulation, complementary alternative medicines, pooled-analysis, meta-analysis, and network-analysis. Bibliographies of the identified articles were manually searched for additional citations not identified in the original search.
CONSENSUS PROCESS: A consensus meeting comprising all representatives took place on September 25-26, 2015, in Tampa, Florida. Guiding principles (eg, emphasis on the most rigorous evidence for efficacy, safety, and tolerability) were discussed, defined, and operationalized prior to review of extant data. As MDD often pursues a recurrent and chronic course, principles of practice, measurement-based care, and comprehensive assessment and management of overall physical and mental health were emphasized. Evidence supporting pretreatment major depressive episode specifiers (eg, mixed features, anxious distress) and the role of pharmacogenomics (and other biological-behavioral markers) in informing treatment selection were comprehensively discussed. Algorithmic priority was assigned to agents with relatively greater therapeutic index (ie, efficacy) and minimal propensity for safety and tolerability disadvantages.
CONCLUSIONS: The updated 2015 FPG provide concise, pragmatic, evidence-based decision support for treatment selection and sequencing for adults with MDD. Principles of practice include measurement-based care, priority to both psychiatric and medical comorbidity, identification of DSM-5-defined specifiers (eg, mixed features), suicide risk assessment, and evaluation of cognitive symptoms. The FPG have purposefully aimed to minimize emphasis on "expert opinion" and instead differentially emphasized extant evidence for pharmacologic treatments.

PMID: 28682531 [PubMed - in process]

The Relationship of Genetics, Nursing Practice, and Informatics Tools in 6-Mercaptopurine Dosing in Pediatric Oncology.

J Pediatr Oncol Nurs. 2017 Jul 01;:1043454217713446

Authors: Haylett WJ

Abstract
An antileukemic agent prescribed for pediatric oncology patients during the maintenance phase of therapy for acute lymphoblastic leukemia, 6-mercaptopurine (6-MP), is highly influenced by genetic variations in the thiopurine S-methyltransferase enzyme. As such, 6-MP must be dosed so that patients with 1 or 2 inactive thiopurine S-methyltransferase alleles will not incur an increased risk for myelosuppression or other toxicities. Informatics tools such as clinical decision support systems are useful for the application of this and similar pharmacogenetics information to the realm of nursing and clinical practice for safe and effective patient care. This article will discuss pharmacogenetics and the associated use of 6-MP; present implications for nursing practice; identify informatics tools such as clinical decision support systems, which can greatly enhance the care of patients whose treatment is based on critical genetic information; and examine the relationship of genetics, nursing practice, and informatics for 6-MP dosing in pediatric oncology.

PMID: 28681659 [PubMed - as supplied by publisher]

Proposal for a Pharmacogenetic Decision Algorithm.

Cureus. 2017 May 30;9(5):e1289

Authors: Alzghari SK, Blakeney L, Rambaran KA

Abstract
Personalized medicine is playing an ever-increasing role in patient care. Over the past decade, awareness of the role of pharmacogenetics and its benefits is leading to its growing acceptance among providers. Though providers are using pharmacogenetics in practice, the decision-making process of when to use this tool can be ambiguous. Herein, we propose an algorithm to help guide providers on when to use pharmacogenetics for patient care.

PMID: 28680777 [PubMed - in process]

Bioavailability and pharmacokinetic comparison of tanshinones between two formulations of Salvia miltiorrhiza in healthy volunteers.

Sci Rep. 2017 Jul 05;7(1):4709

Authors: Xing L, Tan ZR, Cheng JL, Huang WH, Zhang W, Deng W, Yuan CS, Zhou HH

Abstract
Salvia miltiorrhiza (SM) is widely used to treat microcirculatory disturbance-related diseases; its lipophilic components play important roles in this application. Cryptotanshinone (CTS), tanshinone I (TSI) and tanshinone IIA (TSA) are the most widely-studied lipophilic ingredients, but low oral bioavailability limits their clinical application. It has been proven that micronization could improve the bioavailability of some drugs, so we've conducted this randomized study to investigate whether micronized granular powder (GP) of SM could improve the bioavailability of tanshinones compared with traditional decoction (TD). An oral dose of TD or GP of SM was administrated to subjects and blood samples were collected at predetermined time points. The plasma concentrations of tanshinones were detected by a validated method and pharmacokinetic parameters were calculated using a non-compartmental model. GP of SM resulted in a significant increase in mean maximum plasma concentration (C max ), elimination half-life and area under concentration-time curve (AUC) of tanshinones, with the plasma AUC of CTS, TSI and TSA in GP 5-184, 4-619 and 5-130 times higher than TD. In addition, the individual variances of C max and AUC were much lower after GP administration. Summarily, tanshinones in micronized GP of SM had higher oral bioavailability and lower individual variances, thus we speculate that it may indicate a better clinical efficacy and be a better choice than current treatments.

PMID: 28680091 [PubMed - in process]

Air trapping in early cystic fibrosis lung disease-Does CT tell the full story?

Pediatr Pulmonol. 2017 Jul 06;:

Authors: Rosenow T, Ramsey K, Turkovic L, Murray CP, Mok LC, Hall GL, Stick SM, AREST CF

Abstract
INTRODUCTION: Mosaic attenuation on expiratory chest computed tomography (CT) is common in early life cystic fibrosis (CF) and often referred to as "air trapping". It is presumed to be localized hyperinflation due to small airway obstruction. In order to test this assumption, we compared air trapping extent to lung volumes measured on CT in young children with CF.
MATERIALS AND METHODS: Children aged below 7 years undergoing inspiratory/expiratory CT were recruited from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis cohort. Automated lung segmentation was used to determine functional residual capacity (FRC), total lung capacity (TLC), and their ratio (FRC/TLC). Structural lung disease (%Disease) and air trapping (%TrappedAir) extent were assessed using PRAGMA-CF. Lung clearance index (LCI), an index of ventilation heterogeneity, was measured. Linear mixed model analysis was used to determine associations.
RESULTS: Seventy-three scans from 55 patients were obtained. %TrappedAir was associated with %Disease (0.19 [0.07, 0.31]; P = 0.003) and LCI (0.22 [0.04, 0.39]; P = 0.016), but not FRC/TLC (0.00 [-0.02, 0.02]; P = 0.931).
DISCUSSION: CT mosaic attenuation is associated with CF lung disease, however it is not always accompanied by physiologic hyperinflation. Other pathologies may contribute to mosaic attenuation. A better understanding of these factors could guide future therapies.

PMID: 28682006 [PubMed - as supplied by publisher]

An outbreak of Burkholderia cepacia complex in the paediatric unit of a tertiary care hospital.

Indian J Med Microbiol. 2017 Apr-Jun;35(2):216-220

Authors: Mali S, Dash L, Gautam V, Shastri J, Kumar S

Abstract
INTRODUCTION: Burkholderia cepacia complex (Bcc) has emerged as a serious nosocomial pathogen worldwide especially in patients with indwelling catheters and cystic fibrosis. Bcc is a common contaminant of pharmaceutical products. We describe an outbreak of Bcc bacteraemia amongst children admitted in Paediatric Intensive Care Unit (PICU) and paediatric ward at a tertiary care hospital, Mumbai, in Western India.
MATERIALS AND METHODS: Blood culture samples from paediatric patients yielded growth of non-fermenting, oxidase positive, motile, Gram negative bacilli (NFGNB) (76/909) over a period of 8 months. Based on conventional biochemical tests and antimicrobial susceptibility testing, these isolates were provisionally identified as Bcc. The increased, repeated and continued isolation of Bcc alerted the possibility of an outbreak confined to PICU and paediatric ward. Active surveillance was undertaken to trace the source and contain the outbreak. Isolates were subjected to recA polymerase chain reaction (PCR) and Expanded multilocus sequence typing (EMLST).
RESULTS: Surveillance revealed the presence of Bcc on the upper surface of rubber stopper of sealed multidose amikacin vials. Isolates from blood culture and rubber stoppers were confirmed as Bcc by recA PCR. EMLST revealed that these isolates shared an identical novel sequence type 824 proving clonality. Timely interventions instituted led to control of the outbreak.
CONCLUSION: This study highlights the importance of identification and molecular characterization of Bcc to establish its role in infection and outbreak.

PMID: 28681809 [PubMed - in process]

Biofilm-Induced Type 2 Innate Immunity in a Cystic Fibrosis Model of Pseudomonas aeruginosa.

Front Cell Infect Microbiol. 2017;7:274

Authors: Bielen K, 's Jongers B, Boddaert J, Raju TK, Lammens C, Malhotra-Kumar S, Jorens PG, Goossens H, Kumar-Singh S

Abstract
Biofilm-producing strains of Pseudomonas aeruginosa are a major cause of morbidity and mortality in cystic fibrosis (CF) patients. In these patients, increased levels of IL-17 as well as of IL-5 and IL-13 along with arginase (Arg)-positive macrophages have been observed in bronchoalveolar lavage fluid. While IL-17 is a strong proinflammatory cytokine associated with host defense against bacterial and fungal infections and is also elevated in several autoimmune diseases, IL-5/IL-13 and Arg1-positive M2 macrophages are part of the anti-inflammatory type 2 (Th2) immunity. To study whether increased IL-5 and IL-13 levels are related to biofilm formation, which is frequently observed in CF patients colonized by P. aeruginosa, we utilized an agarose bead-embedded P. aeruginosa rat model commonly employed in in vivo biofilm studies. We showed that "sterile" agarose bead instillation in rat notably increased lung transcript levels of IL-5 and IL-13 at two post-instillation study-points, day 1 and day 3. Concurrently, increased infiltration of type 2 innate cells such as eosinophils and Arg1 positive M2 activated macrophages (Arg1+CD68+) was also observed both at day 1 and day 3 while the proportion of M1 activated macrophages (iNOS+CD68+) at these time-points decreased. In contrast, P. aeruginosa-loaded beads caused a drastic elevation of proinflammatory Th1 (IFNγ, TNFα, IL-12a) and antibacterial Th17 (IL-17a, IL-17f, IL-22, IL-23a) cytokines along with a high influx of neutrophils and M1 macrophages, while Th2 cytokines (IL-5 and IL-13) drastically declined at day 1 post-infection. Interestingly, at day 3 post-infection, both Th1 and Th17 cytokines sharply declined and corroborated with decreased M1 and increased M2 macrophages. These data suggest that while IL-17 is linked to episodes of acute exacerbations of infection in CF patients, the increased Th2 cytokines and M2 macrophages observed in these patients are largely due to the biofilm matrix. The data presented here has important implications for clinical management of CF patients.

PMID: 28680858 [PubMed - in process]

Molecular Simulations of Carbohydrates with a Fucose-Binding Burkholderia ambifaria Lectin Suggest Modulation by Surface Residues Outside the Fucose-Binding Pocket.

Front Pharmacol. 2017;8:393

Authors: Dingjan T, Imberty A, Pérez S, Yuriev E, Ramsland PA

Abstract
Burkholderia ambifaria is an opportunistic respiratory pathogen belonging to the Burkholderia cepacia complex, a collection of species responsible for the rapidly fatal cepacia syndrome in cystic fibrosis patients. A fucose-binding lectin identified in the B. ambifaria genome, BambL, is able to adhere to lung tissue, and may play a role in respiratory infection. X-ray crystallography has revealed the bound complex structures for four fucosylated human blood group epitopes (blood group B, H type 1, H type 2, and Le(x) determinants). The present study employed computational approaches, including docking and molecular dynamics (MD), to extend the structural analysis of BambL-oligosaccharide complexes to include four additional blood group saccharides (A, Le(a), Le(b), and Le(y)) and a library of blood-group-related carbohydrates. Carbohydrate recognition is dominated by interactions with fucose via a hydrogen-bonding network involving Arg15, Glu26, Ala38, and Trp79 and a stacking interaction with Trp74. Additional hydrogen bonds to non-fucose residues are formed with Asp30, Tyr35, Thr36, and Trp74. BambL recognition is dominated by interactions with fucose, but also features interactions with other parts of the ligands that may modulate specificity or affinity. The detailed computational characterization of the BambL carbohydrate-binding site provides guidelines for the future design of lectin inhibitors.

PMID: 28680402 [PubMed - in process]

Proteomic profile of cystic fibrosis sputum cells in adults chronically infected with Pseudomonas aeruginosa.

Eur Respir J. 2017 Jul;50(1):

Authors: Pattison SH, Gibson DS, Johnston E, Peacock S, Rivera K, Tunney MM, Pappin DJ, Elborn JS

Abstract
Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection and perturbed immune responses. Tissue damage is mediated mostly by extracellular proteases, but other cellular proteins may also contribute to damage through their effect on cell activities and/or release into sputum fluid by means of active secretion or cell death.We employed MudPIT (multidimensional protein identification technology) to identify sputum cellular proteins with consistently altered abundance in adults with CF, chronically infected with Pseudomonas aeruginosa, compared with healthy controls. Ingenuity Pathway Analysis, Gene Ontology, protein abundance and correlation with lung function were used to infer their potential clinical significance.Differentially abundant proteins relate to Rho family small GTPase activity, immune cell movement/activation, generation of reactive oxygen species, and dysregulation of cell death and proliferation. Compositional breakdown identified high abundance of proteins previously associated with neutrophil extracellular traps. Furthermore, negative correlations with lung function were detected for 17 proteins, many of which have previously been associated with lung injury.These findings expand our current understanding of the mechanisms driving CF lung disease and identify sputum cellular proteins with potential for use as indicators of disease status/prognosis, stratification determinants for treatment prescription or therapeutic targets.

PMID: 28679606 [PubMed - in process]

Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport.

Expert Opin Ther Targets. 2017 Jul 06;:

Authors: Zhang J, Karimy JK, Delpire E, Kahle KT

Abstract
INTRODUCTION: The mammalian SPS1-related proline/alanine-rich serine-threonine kinase SPAK (STK39) modulates the transport across and between epithelial cells in response to environmental stimuli such osmotic stress and inflammation. Research over the last decade has established a central role for SPAK in the regulation of ion and water transport in the distal nephron, colonic crypts, and pancreatic ducts, and has implicated deregulated SPAK signaling in NaCl-sensitive hypertension, ulcerative colitis and Crohn's disease, and cystic fibrosis. Areas covered: We review recent advances in our understanding of the role of SPAK kinase in the regulation of epithelial transport. We highlight how SPAK signaling - including its upstream Cl(-)sensitive activators, the WNK kinases, and its downstream ion transport targets, the cation- Cl(-)cotransporters contribute to human disease. We discuss prospects for the pharmacotherapeutic targeting of SPAK kinase in specific human disorders that feature impaired epithelial homeostasis. Expert opinion: The development of novel drugs that antagonize the SPAK-WNK interaction, inhibit SPAK kinase activity, or disrupt SPAK kinase activation by interfering with its binding to MO25α/β could be useful adjuncts in essential hypertension, inflammatory colitis, and cystic fibrosis.

PMID: 28679296 [PubMed - as supplied by publisher]

Association of NOD2 Mutations with Aggressive Periodontitis.

J Dent Res. 2017 Jun 01;:22034517715432

Authors: Sudo T, Okada Y, Ozaki K, Urayama K, Kanai M, Kobayashi H, Gokyu M, Izumi Y, Tanaka T

Abstract
Aggressive periodontitis (AgP) is characterized by rapid alveolar bone destruction and tooth loss early in life, and its etiology remains unclear. To explore the genetic risk factors of AgP, we performed genome-wide single-nucleotide polymorphism genotyping for identity-by-descent mapping and identified 32 distinct candidate loci, followed by whole exome sequencing with 2 pedigrees of AgP consisting of 3 cases and 1 control in 1 family and 2 sibling cases in the other. After variant filtering procedures and validation by targeted Sanger sequencing, we identified 2 missense mutations at 16q12 in NOD2 (p.Ala110Thr and p.Arg311Trp), which encodes nucleotide-binding oligomerization domain protein 2. We further examined 94 genetically unrelated AgP patients by targeted sequencing of NOD2 and found that 2 patients among them also carried the p.Arg311Trp variant. Furthermore, we found 3 additional missense mutations in this gene (p.His370Tyr, p.Arg459Cys, and p.Ala868Thr). These mutations either had not been previously observed or are extremely rare (frequency <0.001) in Asian populations. NOD2 plays a crucial role in innate immunity as an intracellular receptor initiating nuclear factor κB-dependent and mitogen-activated protein kinase-dependent gene transcription. These results demonstrated NOD2 as a novel gene involved in AgP.

PMID: 28682159 [PubMed - as supplied by publisher]