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- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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- Berggren, A M, et al.
(författare)
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Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats
- 1996
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Ingår i: British Journal of Nutrition. - 0007-1145. ; 76:2, s. 94-287
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Tidskriftsartikel (refereegranskat)abstract
- It has increasingly been suggested that the short-chain fatty acids (SCFA) acetic, propionic and butyric acids, derived from colonic fermentation of dietary fibre and other indigestible carbohydrates, exert different physiological effects. Formation of propionic acid is discussed in terms of beneficial effects on glucose and cholesterol metabolism. The aim of the present study was to evaluate possible metabolic effects of propionic acid and to differentiate between effects mediated in the upper gastrointestinal tract and those mediated in the hind-gut. For this purpose, obese hyperinsulinaemic (fa/fa) rats were studied during a 19 d test period. Sodium propionate was either fed orally through the diet (1 g/d), or infused rectally (0.15 g/d) to animals given diets high in cholesterol (20 g/kg) and saturated fat (130 g/kg). At the end of the test period total liver cholesterol pools were 20% lower (P < 0.01) in rats given dietary or rectally infused propionate (481 and 484 mg respectively) compared with the control group (614 mg). This was due to lower liver weights (P < 0.05) in propionate-treated animals, 15.5 and 15.3 g, v. 18.2 g in the control group, and no differences were noted in hepatic cholesterol concentrations. The urinary glucose excretion was measured during days 15-19 and was found to be lower (P < 0.05) in rats fed with propionate (23 mg) compared with the control group or the group infused rectally (39 and 38 mg respectively). In addition, fasting plasma glucose concentrations decreased significantly (P < 0.05) over the test period. It is concluded that orally supplied propionate affects both glucose and cholesterol metabolism as judged from lowered urinary glucose excretion, fasting blood glucose and liver cholesterol pools. On the other hand, propionate administered to the hind-gut at a physiologically relevant level reduces the hepatic cholesterol pool.
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- Budtz-Lilly, Jacob, et al.
(författare)
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Editor's Choice - Assessment of International Outcomes of Intact Abdominal Aortic Aneurysm Repair over 9 Years
- 2017
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 54:1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Case mix and outcomes of complex surgical procedures vary over time and between regions. This study analyses peri-operative mortality after intact abdominal aortic aneurysm (AAA) repair in 11 countries over 9 years. Methods: Data on primary AAA repair from vascular surgery registries in 11 countries for the years 2005-2009 and 2010-2013 were analysed. Multivariate adjusted logistic regression analyses were carried out to adjust for variations in case mix. Results: A total of 83,253 patients were included. Over the two periods, the proportion of patients >= 80 years old increased (18.5% vs. 23.1%; p < .0001) as did the proportion of endovascular repair (EVAR) (44.3% vs. 60.6; p < .0001). In the latter period, 25.8% of AAAs were less than 5.5 cm. The mean annual volume of open repairs per centre decreased from 12.9 to 10.6 between the two periods (p < .0001), and it increased for EVAR from 10.0 to 17.1 (p < .0001). Overall, peri-operative mortality fell from 3.0% to 2.4% (p < .0001). Mortality for EVAR decreased from 1.5% to 1.1% (p < .0001), but the outcome worsened for open repair from 3.9% to 4.4% (p = .008). The peri-operative risk was greater for octogenarians (overall, 3.6% vs. 2.1%, p < .0001; open, 9.5% vs. 3.6%, p < .0001; EVAR, 1.8% vs. 0.7%, p < .0001), and women (overall, 3.8% vs. 2.2%, p < .0001; open, 6.0% vs. 4.0%, p < .0001; EVAR, 1.9% vs. 0.9%, p < .0001). Peri-operative mortality after repair of AAAs <5.5 cm was 4.4% with open repair and 1.0% with EVAR, p < .0001. Conclusions: In this large international cohort, total peri-operative mortality continues to fall for the treatment of intact AAAs. The number of EVAR procedures now exceeds open procedures. Mortality after EVAR has decreased, but mortality for open operations has increased. The peri-operative mortality for small AM treatment, particularly open surgical repair, is still considerable and should be weighed against the risk of rupture.
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| 8. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 10. |
- Sloth, B, et al.
(författare)
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No difference in body weight decrease between a low-glycemic-index and a high-glycemic-index diet but reduced LDL cholesterol after 10-wk ad libitum intake of the low-glycemic-index diet
- 2004
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 80:2, s. 337-347
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of glycemic index (GI) in appetite and body-weight regulation is still not clear. Objective: The objective of the study was to investigate the long-term effects of a low-fat, high-carbohydrate diet with either low glycemic index (LGI) or high glycemic index (HGI) on ad libitum energy intake, body weight, and composition, as well as on risk factors for type 2 diabetes and ischemic heart disease in overweight healthy subjects. Design: The study was a 10-wk parallel, randomized, intervention trial with 2 matched groups. The LGI or HGI test foods, given as replacements for the subjects’ usual carbohydrate-rich foods, were equal in total energy, energy density, dietary fiber, and macronutrient composition. Subjects were 45 (LGI diet: n = 23; HGI diet: n = 22) healthy overweight [body mass index (in kg/m2): 27.6 ± 0.2] women aged 20–40 y. Results: Energy intake, mean (± SEM) body weight (LGI diet: –1.9 ± 0.5 kg; HGI diet: –1.3 ± 0.3 kg), and fat mass (LGI diet: –1.0 ± 0.4 kg; HGI diet: –0.4 ± 0.3 kg) decreased over time, but the differences between groups were not significant. No significant differences were observed between groups in fasting serum insulin, homeostasis model assessment for relative insulin resistance, homeostasis model assessment for ß cell function, triacylglycerol, nonesterified fatty acids, or HDL cholesterol. However, a 10% decrease in LDL cholesterol (P < 0.05) and a tendency to a larger decrease in total cholesterol (P = 0.06) were observed with consumption of the LGI diet as compared with the HGI diet. Conclusions: This study does not support the contention that low-fat LGI diets are more beneficial than HGI diets with regard to appetite or body-weight regulation as evaluated over 10 wk. However, it confirms previous findings of a beneficial effect of LGI diets on risk factors for ischemic heart disease. Key Words: Obesity • fat mass • energy intake • type 2 diabetes • ischemic heart disease • cholesterol • triacylglycerol • glucose • insulin
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