Marieke J H Coenen's research while affiliated with Radboud University Medical Centre (Radboudumc) and other places

Publications (111)

Article
Full-text available
Background Clopidogrel is recommended in international guidelines to prevent arterial thrombotic events in patients with peripheral arterial disease (PAD). Clopidogrel itself is inactive and metabolism is dependent on the CYP2C19 enzyme. About 30% of Caucasian PAD patients receiving clopidogrel carry one or two CYP2C19 loss-of-function allele(s) an...
Preprint
Full-text available
Drug treatment for nociceptive musculoskeletal pain (NMP) follows a three-step analgesic ladder proposed by the World Health Organization (WHO), starting from non-steroidal anti-inflammatory drugs (NSAIDs), followed by weak or strong opioids until the pain is under control. However, effective pain treatment is challenged by inter-individual differe...
Conference Paper
Full-text available
Background The interplay between genetics and drug response in rheumatoid arthritis (RA) has shown that response to biologics varies between individuals and that a large proportion of patients show no clinical improvement (Plenge and Bridges, 2011). Despite the disappointing scenario, to date, only a few genetic markers have been consistently ident...
Article
Full-text available
Background A debilitating late effect for childhood cancer survivors (CCS) is cancer-related fatigue (CRF). Little is known about the prevalence and risk factors of fatigue in this population. Here we describe the methodology of the Dutch Childhood Cancer Survivor Late Effect Study on fatigue (DCCSS LATER fatigue study). The aim of the DCCSS LATER...
Article
Background: Myotonic dystrophy type 2 (DM2) is caused by a CCTG repeat expansion in intron 1 of the CCHC-Type Zinc Finger Nucleic Acid Binding Protein (CNBP) gene. Previous studies indicated that this repeat expansion originates from separate founders. Objective: This study was set out to determine whether or not patients with DM2 originating fr...
Article
Full-text available
Neuroleptic malignant syndrome and serotonin syndrome are two syndromes whose molecular bases remain poorly understood. The phenotypes of both syndromes overlap with other syndromes that have a clear genetic background, in particular RYR1-related malignant hyperthermia. Through a literature review, performed according to the PRISMA guidelines, we a...
Article
Full-text available
Purpose To develop a genotype assay to assess associations with common and rare AMD risk variants, to calculate an overall genetic risk score (GRS), and to identify potential misdiagnoses with inherited macular dystrophies that mimic AMD. Design Case-control study. Participants Individuals (N=4,740) from five European cohorts. Methods We designe...
Article
Full-text available
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10⁻¹²) and IRF4 (rs9405192, OR = 1.29, P = 1.4 ×...
Article
Full-text available
Background: Genetic predictors for treatment response could optimize allocation of biological treatment in patients with psoriasis. There is minimal knowledge about pharmacogenetics of anti-IL17 agents. Objectives: To assess whether genetic variants in the protein-coding region or untranslated regions of the IL17A gene are associated with respon...
Article
Full-text available
Ototoxicity and nephrotoxicity are potentially irreversible side effects of chemoradiotherapy with cisplatin in locally advanced head and neck cancer (LAHNC) patients. Several predictive genetic variants have been described, but as yet none in LAHNC patients. The aim of this study is to investigate genetic variants as predictors for ototoxicity and...
Article
Importance Previous research showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis but consisted mostly of small (and sometimes inconclusive) cohort studies. Objective To assess whether HLA-C*06:02 status is associated with a differential response to ustekinumab therapy in patients with psoria...
Article
Full-text available
The aim of this case-control study was to evaluate whether 47 single nucleotide polymorphisms (SNPs) in steroid hormone-related genes are associated with the risk of RA and anti-TNF drug response. We conducted a case-control study in 3 European populations including 2936 RA patients and 2197 healthy controls. Of those a total of 1985 RA patients we...
Article
Full-text available
Objective Fluoropyrimidine treatment can be optimized based on dihydropyrimidine dehydrogenase (DPD) activity. DPD dysfunction leads to increased exposure to active metabolites, which can result in severe or even fatal toxicity. Methods We provide an overview of 8 years of DPD diagnostic testing (n = 1194). Results Within the study period, our di...
Article
银屑病是一种常见皮肤病,是机体过量产生一种称为“肿瘤坏死因子-α”(TNF-α) 的蛋白质反过来引发炎症的情形。生物制剂是相对新型的强效药物,能够降低 TNF-α 活性,可用于治疗中度到重度的银屑病。目前有很多不同类型的生物制剂,寻找最适合个体患者的生物制剂是一个反复试验的过程,可能在很长一段时间里治疗结果不如预期的那么好,而且需要投入大量不必要的成本。基因差异(遗传变异)可能解释为何生物制剂的效果因人而异,并且有助于预测特效生物制剂是否可能对患者有效。该医学领域被称为药物遗传学。这项在荷兰开展的研究对其他发表的研究进行了综述,旨在了解遗传变异与使用不同生物制剂的疗效之间的关联。该综述涵盖了 26 项研究,探讨了阿达木单抗、依那西普、英夫利昔单抗以及优特克单抗生物制剂。未找到苏金单抗或伊赛珠...
Article
Psoriasis is a common skin disease in which the body produces too much of a protein called ‘tumour necrosis factor alpha’ (TNF-alpha) which in turn causes inflammation. Biologics are relatively new, powerful drugs used for treating moderate to severe psoriasis due to their ability to reduce the activity of TNF-alpha. There are several different typ...
Article
Background: Biologics are indicated for treating moderate-to-severe psoriasis. As the number of biologics registered for the treatment of psoriasis increases, so does the need for biomarkers to guide personalized therapeutic decisions. Genetic variants might serve as predictors for treatment response, a field of research known as pharmacogenetics....
Article
Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a f...
Article
The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-...
Article
Background: Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations. Aim: To determine the predictive value of 6-MMPR concentrations 1 week a...
Article
Background: The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. Objectives: We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohor...
Article
In osteosarcoma, large variation is observed in the efficacy and toxicity of chemotherapeutic drugs among similarly treated patients. Treatment optimization using predictive factors or algorithms is of importance, because there has been a lack of improvement of treatment outcome and survival for decades. The outcome of cancer treatment is influence...
Article
Objective: Irreversible hearing loss is a frequent side effect of the chemotherapeutic agent cisplatin and shows considerable interpatient variability. The variant rs1872328 in the ACYP2 gene was recently identified as a risk factor for the development of cisplatin-induced ototoxicity in children with brain tumors. We aimed to replicate this findi...
Article
Introduction: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C<T loss-of-function variant of AMPD1 (rs17602729) is associated with incr...
Article
It is likely that hypoglycaemia unawareness (HU) is in part determined by genetic factors. In a small cohort, we found that a single nucleotide polymorphsim (SNP) of the gene encoding the β2-adrenergic receptor (ADRB2) was associated with HU in patients with type 1 diabetes (T1D). Genes that have been associated with the incidence of severe hypogly...
Article
Full-text available
Purpose: Overall survival in patients with osteosarcoma is only 60%. Poor response to chemotherapy is the dominant risk factor for poor survival. Pharmacogenetic research can offer possibilities to optimize treatment and improve outcome. We applied a pathway-based approach to evaluate the cumulative effect of genes involved in the metabolism of ci...
Article
During coronary artery bypass graft (CABG) surgery, ischaemia and reperfusion damage myocardial tissue, and increased postoperative plasma troponin concentration is associated with a worse outcome. We investigated whether metformin pretreatment limits cardiac injury, assessed by troponin concentrations, during CABG surgery in patients without diabe...
Article
More than 20% of patients with inflammatory bowel disease (IBD) discontinue thiopurine therapy due to severe adverse drug reactions (ADRs); leucopenia is one of the most serious ADRs. Variants in the gene encoding thiopurine S-methyltransferase (TPMT) alter its enzymatic activity, resulting in higher levels of thiopurine metabolites, which can caus...
Article
Full-text available
Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk...
Article
Dipyridamole reduces reperfusion-injury in preclinical trials and may be beneficial in patients undergoing coronary angioplasty, but its effect in patients undergoing coronary artery bypass grafting (CABG) is unknown. We hypothesized that dipyridamole limits myocardial reperfusion-injury in patients undergoing CABG. Double-blind trial randomizing b...
Article
The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array covers 1936 markers in 231 genes involved in drug metabolism and transport. Blood- and saliva-derived DNA works well on the DMET array, but the utility of DNA from FFPE tissue has not been reported for this array. As the ability to use DNA from FFPE tissue on the array coul...
Article
Full-text available
Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual varia...
Article
Objectives Pharmacogenetic studies of tumour necrosis factor inhibitors (TNFi) response in patients with rheumatoid arthritis (RA) have largely relied on the changes in complex disease scores, such as disease activity score 28 (DAS28), as a measure of treatment response. It is expected that genetic architecture of such complex score is heterogeneou...
Article
Full-text available
Background Activating mutations in the Transient Receptor Potential channel C6 (TRPC6) cause autosomal dominant focal segmental glomerular sclerosis (FSGS). TRPC6 expression is upregulated in renal biopsies of patients with idiopathic membranous glomerulopathy (iMN) and animal models thereof. In iMN, disease progression is characterized by glomerul...
Article
Background: X-linked sideroblastic anaemia (XLSA; OMIM#300751) is the most common inherited form of sideroblastic anaemia and is associated with several mutations in the erythroid specific 5-aminolevulinate synthase gene (ALAS₂). This gene encodes for aminolevulinic acid synthase 2 (ALAS₂), the catalytic enzyme involved in the first en rate-limiti...
Article
Full-text available
Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gen...
Article
Full-text available
Methotrexate (MTX), one of the important pillars in the treatment of different forms of cancer, is associated with the development of hepatotoxicity. The 677C>T variant (rs1801133) in the methylenetetrahydrofolate reductase (MTHFR) gene might affect the development of hepatotoxicity. Results in literature are, however, contradictive. The aim of thi...
Article
Full-text available
Author Summary There are no genetic predictors of response to one of the most widely used classes of drugs in the treatment of rheumatoid arthritis—biological modifiers of the inflammatory cytokine tumor necrosis factor-alpha (or anti-TNF therapy). To identify genetic predictors, we performed the largest genome-wide association study (GWAS) to dat...
Article
Full-text available
Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis...
Article
Full-text available
Introduction: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with inc...
Article
Full-text available
The M-type receptor for phospholipase A2 (PLA2R1) is the major target antigen in idiopathic membranous nephropathy (iMN). Our recent genome-wide association study showed that genetic variants in an HLA-DQA1 and phospholipase A2 receptor (PLA2R1) allele associate most significantly with biopsy-proven iMN, suggesting that rare genetic variants within...
Article
Full-text available
Background: Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic...
Article
Full-text available
The c-Src tyrosine kinase, Csk, physically interacts with the intracellular phosphatase Lyp (encoded by PTPN22) and can modify the activation state of downstream Src kinases, such as Lyn, in lymphocytes. We identified an association of CSK with systemic lupus erythematosus (SLE) and refined its location to the intronic polymorphism rs34933034 (odds...
Article
Full-text available
So far, there are no means of identifying rheumatoid arthritis (RA) patients who will fail to respond to tumour necrosis factor blocking agents (anti-TNF), prior to treatment. We set out to validate eight previously reported gene expression signatures predicting therapy outcome. Genome-wide expression profiling using Affymetrix GeneChip Exon 1.0 ST...
Article
Full-text available
Two recent studies, in a Spanish and a Chinese population, point to an association between rheumatoid arthritis (RA) risk and the deletion of the Late Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor for psoriasis. We aimed to replicate these studies in a large Dutch cohort. 1039 RA cases and 759 controls were genotyp...
Article
Full-text available
To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consis...
Article
Full-text available
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune cell activation, and fibrosis of the skin and internal organs. Over the past few years, a role for genetics in the susceptibility for SSc has been established. This review aims to provide an update on the progress made in the past year or so within the field of...
Article
Full-text available
A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed...
Article
The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region. We ana...
Article
Systemic sclerosis (SSc) is a severe autoimmune connective tissue disease. Over the years, evidence for a genetic background of SSc susceptibility has clearly accumulated. This article aims to provide an extensive overview of genetics in SSc research. We discuss indicators for a genetic component present in SSc, family studies, chromosomal aberranc...
Article
Full-text available
The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromer...
Article
The aim of the present study was to replicate the previously reported association of KLF12 gene polymorphisms with rheumatoid arthritis (RA). Two independent cohorts from Spain (1,360 RA patients and 1,520 controls) and the Netherlands (1,018 RA patients and 1,150 controls) were genotyped for KLF12 rs1887346 and rs9565072 single-nucleotide polymorp...