| 1. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 2. |
- Eriksson, Daniel, et al.
(författare)
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Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.
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| 3. |
- Kofteridis, Diamantis P., et al.
(författare)
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Treatment pattern, prognostic factors, and outcome in patients with infection due to pan-drug-resistant gram-negative bacteria
- 2020
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 39:5, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the clinical course, treatment pattern, prognostic factors, and outcome of patients with pun-drug resistant (PDR) infections. This was a retrospective single-center cohort study including consecutive eligible patients with a PDR infection hospitalized at the University Hospital of Heraklion, Crete, Greece, between January 2010 and June 2018. In total, 65 patients with infections due to PDR gram-negative pathogens were identified. The median age was 64 years (interquartile range, IQR: 45.5-74.5) and the median Charlson comorbidity index 3.0 (IQR: 1.0-5.75). Of the 65 PDR isolates, 31 (48%) were Klebsiella pneumoniae, 28 (43%) Acinetobacter baumannii, and 6 (9%) Pseudomonas aeruginosa. The most common empirical therapy was colistin-based combination (n = 32; 49%), followed by non-colistin, non-tigecycline combination (n = 25; 39%), and carbapenemes + tigecycline (n = 8; 12%). The empirical therapy was effective in 50%, 37.5%, and 8% of patients receiving colistin combination, carbapenemes - tigecycline, and non-colistin, non-tigecycline combination, respectively (p value = 0.003). The infection-related in-hospital mortality was 32% (95% confidence interval, CI: 21-45%). Three factors were significantly associated with infection-related in-hospital mortality in multivariate analysis: Charlson comorbidity index (odds ratio, OR: 1.5, 95% CI: 1.0-2.3, p value = 0.030), prior steroid use (OR: 4.1, 95% CI: 1.0-17.0, p value = 0.049), and empirical treatment with non-colistin, non-tigecycline combination (OR: 7.5; 95% CI: 1.7-32.8, p value = 0.008). Infections due to PDR pathogens are associated with considerable mortality. Our results support the use of colistin and/or tigecycline-based combinations as empirical therapy when infection due to PDR pathogens is suspected.
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