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- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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- Hess, Timo, et al.
(author)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Journal article (peer-reviewed)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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- Johansson, Maria U, et al.
(author)
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Structure, specificity, and mode of interaction for bacterial albumin-binding modules.
- 2002
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In: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 277:10, s. 8114-8120
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Journal article (peer-reviewed)abstract
- We have determined the solution structure of an albumin binding domain of protein G, a surface protein of group C and G streptococci. We find that it folds into a left handed three-helix bundle similar to the albumin binding domain of protein PAB from Peptostreptococcus magnus. The two domains share 59% sequence identity, are thermally very stable, and bind to the same site on human serum albumin. The albumin binding site, the first determined for this structural motif known as the GA module, comprises residues spanning the first loop to the beginning of the third helix and includes the most conserved region of GA modules. The two GA modules have different affinities for albumin from different species, and their albumin binding patterns correspond directly to the host specificity of C/G streptococci and P. magnus, respectively. These studies of the evolution, structure, and binding properties of the GA module emphasize the power of bacterial adaptation and underline ecological and medical problems connected with the use of antibiotics.
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- Fridriksson, Johann Fridrik, et al.
(author)
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Working Environment and work retention
- 2017
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Reports (other academic/artistic)abstract
- The project shows that the working environment is rarely the sole cause of early retirement, but working environment factors may explain a large fraction of the transition to disability pension in particular. Several working environment predictors of early retirement are well-documented in the Nordic countries, but workplace policies and activities to retain older workers rarely aim to improve the working environment. There may be great potentials in developing workplace interventions which combine prevention of working environment risk factors (e.g. risk factors for accidents, strenuous work/high physical work demands, insufficient recovery between work shifts, quantitative work demands, conflicts at work and bullying/harassment, and age discrimination) with increment of job satisfaction through increased control/influence, possibilities for development and recognition from management.
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| 7. |
- Hellberg, Maria, et al.
(author)
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Eradication of nasopharyngeal carriage of penicillin-non-susceptible Streptococcus pneumoniae-is it possible?
- 2012
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 44:12, s. 909-914
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Journal article (peer-reviewed)abstract
- Background: The South Swedish Pneumococcal Intervention Project (SSPIP) was started in 1995 with the aim of limiting the spread of penicillin-non-susceptible pneumococci (PNSP) in Skåne County, Sweden. As part of the SSPIP, eradication therapy with rifampicin in combination with 1 more antibiotic was considered on a social indication after prolonged carriage of 2-3 months. Methods: In this retrospective study, 125 medical records were analyzed. Children aged 0-10 y referred for eradication therapy in Malmö and Lund, due to a prolonged nasopharyngeal carriage of PNSP with a penicillin G minimum inhibitory concentration of ≥ 0.5 mg/l, between the y 1997 and 2011 were included. Two consecutive negative cultures, with the second one no shorter than 7 days after treatment completion, were required for the carriage to be considered eradicated. Results: Out of 125 children, 71 received treatment with rifampicin in combination with amoxicillin (n = 44), erythromycin (n = 22), or clindamycin (n = 5) for 7 days. Eradication treatment was successful in 91.5% of the children. Six children (8.5%) had treatment failure with amoxicillin and rifampicin; 3 were found by late follow-up. There was a trend towards a better outcome with erythromycin and clindamycin combinations in comparison to amoxicillin. Conclusions: Eradication therapy was successful, but a proper follow-up is essential.
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- Metzger, Jonathan, et al.
(author)
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Sämre planering ingen lösning
- 2016
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In: Svenska dagbladet. - 1101-2412.
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Journal article (other academic/artistic)
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