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Addison Disease: HELP
Articles by Heather J. Cordell
Based on 6 articles published since 2008
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Between 2008 and 2019, H. Cordell wrote the following 6 articles about Addison Disease.
 
+ Citations + Abstracts
1 Clinical Trial Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus. 2015

Mitchell, Anna L / Bøe Wolff, Anette / MacArthur, Katie / Weaver, Jolanta U / Vaidya, Bijay / Anonymous2910832 / Erichsen, Martina M / Darlay, Rebecca / Husebye, Eystein S / Cordell, Heather J / Pearce, Simon H S. ·Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. · Department of Clinical Science, University of Bergen, Bergen, Norway. · Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. · Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom. · Department of Medicine, Haukeland University Hospital, Bergen, Norway. · Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway. ·PLoS One · Pubmed #26042420.

ABSTRACT: BACKGROUND: Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. METHODS: DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. RESULTS: In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. CONCLUSION: This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

2 Article A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison's Disease in Humans. 2016

Pazderska, Agnieszka / Oftedal, Bergithe E / Napier, Catherine M / Ainsworth, Holly F / Husebye, Eystein S / Cordell, Heather J / Pearce, Simon H S / Mitchell, Anna L. ·Institute of Genetic Medicine (A.P., C.M.N., H.F.A., H.J.C., S.H.S.P., A.L.M.), Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom · Department of Clinical Science (B.E.O., E.S.H.), University of Bergen, 5021 Bergen, Norway · and Department of Medicine (E.S.H.), Haukeland University Hospital, 5021 Bergen, Norway. ·J Clin Endocrinol Metab · Pubmed #27680876.

ABSTRACT: CONTEXT: Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions. OBJECTIVE: We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD. DESIGN, SETTING, AND PATIENTS: This case-control association study was performed in two phases using Taqman chemistry. In the first phase, the rs3757247 SNP was genotyped in 358 UK AAD subjects and 166 local control subjects. Genotype data were also available from 5154 healthy UK controls from the Wellcome Trust (WTCCC2) for comparison. In the second phase, the SNP was genotyped in a validation cohort comprising 317 Norwegian AAD subjects and 365 controls. RESULTS: The frequency of the minor T allele was significantly higher in subjects with AAD from the United Kingdom compared to both the local and WTCCC2 control cohorts (58% vs 45 and 48%, respectively) (local controls, P = 1.1 × 10 CONCLUSION: We have demonstrated, for the first time, that allelic variability at the BACH2 locus is associated with susceptibility to AAD. Given its association with multiple autoimmune conditions, BACH2 can be considered a "universal" autoimmune susceptibility locus.

3 Article CTLA-4 as a genetic determinant in autoimmune Addison's disease. 2015

Wolff, A S B / Mitchell, A L / Cordell, H J / Short, A / Skinningsrud, B / Ollier, W / Badenhoop, K / Meyer, G / Falorni, A / Kampe, O / Undlien, D / Pearce, S H S / Husebye, E S. ·Department of Clinical Science, University of Bergen, Bergen, Norway. · Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. · Centre for Integrated Genomic Medical Research, Institute of Population Health, Manchester University, Manchester, UK. · Institute of Medical Genetics, University of Oslo, Oslo, Norway. · Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. · Department of Endocrinology and Diabetes, Internal Medicine 1, Johann-Wolfgang-Goethe-University's Hospital, Frankfurt, Germany. · Department of Medicine, University of Perugia, Perugia, Italy. · Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. · Department of Medicine, Haukeland University Hospital, Bergen, Norway. ·Genes Immun · Pubmed #26204230.

ABSTRACT: In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.

4 Article Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts. 2014

Mitchell, Anna L / Macarthur, Katie D R / Gan, Earn H / Baggott, Lucy E / Wolff, Anette S B / Skinningsrud, Beate / Platt, Hazel / Short, Andrea / Lobell, Anna / Kämpe, Olle / Bensing, Sophie / Betterle, Corrado / Kasperlik-Zaluska, Anna / Zurawek, Magdalena / Fichna, Marta / Kockum, Ingrid / Nordling Eriksson, Gabriel / Ekwall, Olov / Wahlberg, Jeanette / Dahlqvist, Per / Hulting, Anna-Lena / Penna-Martinez, Marissa / Meyer, Gesine / Kahles, Heinrich / Badenhoop, Klaus / Hahner, Stephanie / Quinkler, Marcus / Falorni, Alberto / Phipps-Green, Amanda / Merriman, Tony R / Ollier, William / Cordell, Heather J / Undlien, Dag / Czarnocka, Barbara / Husebye, Eystein / Pearce, Simon H S. ·Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom. · Department of Clinical Science, University of Bergen, Bergen, Norway. · Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; University of Oslo, Oslo, Norway. · CIGMR, Institute of Population Health, University of Manchester, Manchester, United Kingdom. · Uppsala University, Uppsala, Sweden. · Uppsala University, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden. · Department of Medicine, University of Padua School of Medicine, Padua, Italy. · Department of Endocrinology, Center for Postgraduate Medical Education, Warsaw, Poland. · Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. · Neuroimmunology Unit, Department of Clinical Neuroscience and Centrum for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. · The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Department of Medical and Health Sciences, Division of Endocrinology, Faculty of Health Sciences, Linköping University, Linköping, Sweden. · Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. · Karolinska Institutet, Stockholm, Sweden. · Department Medicine (Division Endocrinology), University Hospital Frankfurt, Goethe-University, Frankfurt, Germany. · University Hospital Wuerzburg (Department of Medicine, Endocrinology and Diabetology), Wuerzburg, Germany. · Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany. · Department of Internal Medicine, University of Perugia, Perugia, Italy. · Department of Biochemistry, University of Otago, Otago, New Zealand. · Department of Biochemistry and Molecular Biology, Center for Postgraduate Medical Education, Warsaw, Poland. · Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway. ·PLoS One · Pubmed #24614117.

ABSTRACT: BACKGROUND: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. AIM: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. METHODS: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. RESULTS: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively. CONCLUSIONS: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.

5 Article Programmed death ligand 1 (PD-L1) gene variants contribute to autoimmune Addison's disease and Graves' disease susceptibility. 2009

Mitchell, Anna L / Cordell, Heather J / Soemedi, Rachel / Owen, Kate / Skinningsrud, Beate / Wolff, Anette Bøe / Ericksen, Martina / Undlien, Dag / Husebye, Eystein / Pearce, Simon H S. ·Institute of Human Genetics, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom. ·J Clin Endocrinol Metab · Pubmed #19850680.

ABSTRACT: CONTEXT: Despite much investigation, a substantial amount of the genetic susceptibility to autoimmune diseases remains unaccounted for. Recently, a single-nucleotide polymorphism (SNP) in the programmed death ligand 1 (PD-L1) gene has been associated with Graves' disease (GD) in a Japanese patient cohort. Our aim was to determine whether variants in PD-L1 are also associated with autoimmune Addison's disease (AAD) and to replicate the previous association in patients with GD from the United Kingdom. DESIGN AND PATIENTS: We analyzed eight SNPs within PD-L1 in a United Kingdom cohort of 315 AAD subjects and 316 healthy controls. We then replicated our experiment in a cohort of 342 Norwegian AAD cases and 379 controls and in 496 United Kingdom GD subjects. RESULTS: Three of the eight SNPs studied, part of a haplotype block in the PD-L1 gene, showed modest association with both AAD and GD in the United Kingdom cohort, with maximum evidence at the marker RS1411262 [United Kingdom AAD odds ratio 1.33 (5-95% confidence interval 1.02-1.73), P(genotype) = 0.028; GD odds ratio 1.36 (5-95% confidence interval 1.07-1.72), P(genotype) = 0.033]. Association with genotypes at the same three markers was confirmed in the Norwegian AAD cohort [P(genotype) = 0.011-0.020]. A recessive effect at the most associated alleles was observed in both the AAD and GD cohorts. CONCLUSIONS: We confirm the role of PD-L1 variants in GD susceptibility and extend these findings to demonstrate association in two Northern European patient cohorts with AAD. PD-L1 joins the growing number of known susceptibility loci exerting modest effects in these autoimmune disorders.

6 Article The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22) gene predisposes to autoimmune Addison's disease. 2009

Roycroft, Matthew / Fichna, Marta / McDonald, David / Owen, Kate / Zurawek, Magdalena / Gryczyńska, Maria / Januszkiewicz-Lewandowska, Danuta / Fichna, Piotr / Cordell, Heather / Donaldson, Peter / Nowak, Jerzy / Pearce, Simon. ·Institute of Human Genetics, Newcastle University, Newcastle Upon Tyne, UK. ·Clin Endocrinol (Oxf) · Pubmed #18710467.

ABSTRACT: OBJECTIVE: Previous studies of the association between autoimmune Addison's disease (AAD) and a nonsynonymous single nucleotide polymorphism (SNP) in the PTPN22 gene (C1858T, pR620W; SNP ID no. rs2476601) have shown conflicting results. We aimed to examine this association using additional cohorts of AAD subjects from the UK and Poland. DESIGN: DNA samples were obtained from UK and Polish AAD subjects (n = 251 and 87, respectively) and ethnically matched healthy controls (n = 429 and 236, respectively). Genotyping for the C1858T PTPN22 marker was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Meta-analysis of the results, together with those from three other populations, was performed using RevMan v5.0 software. RESULTS: In 251 UK AAD subjects the frequency of the PTPN22 1858T allele was 12.2% compared to 7.8% in healthy UK controls; P = 0.008. Similarly, in 87 Polish AAD subjects the PTPN22 1858T allele was found in 19.5% of alleles compared to 11.7% in healthy Polish subjects; P = 0.010. A meta-analysis, combining these result with published data for three other populations, involving 797 AAD subjects and 2032 controls in total, showed that the 1858T allele was associated with AAD susceptibility with a pooled odds ratio (OR) of 1.44 [95% confidence interval (CI) 1.21-1.72; P = 5.6 x 10(-5)], under a fixed-effects model. CONCLUSION: This study confirms the association between the PTPN22 1858T allele and AAD in an expanded UK cohort and in the previously unstudied Polish population. This meta-analysis allows for the first time a reliable estimate of the strength of effect of this autoimmune disease susceptibility allele across different European Caucasian populations.