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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
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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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| 3. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 4. |
- 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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| 6. |
- Berggren, Anna M., et al.
(författare)
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Short‐chain fatty acid content and pH in caecum of rats fed various sources of starch
- 1995
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Ingår i: Journal of the Science of Food and Agriculture. - : Wiley. - 0022-5142 .- 1097-0010. ; 68:2, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- Caecal pH and contents of short‐chain fatty acids (SCFA) were registered in rats fed three potential sources of resistant starch (RS); raw pea starch, raw potato starch, and an RS‐enriched preparation obtained from wheat starch by autoclaving and enzymatic incubation. Small intestinal digestibility and delivery of RS to the hind‐gut in the case of raw starches were determined by analysis of faecal starch in animals treated with antibiotics to prevent hind‐gut fermentation. RS content in the RS‐enriched preparation was determined as total starch remaining in an enzymatic gravimetric dietary fibre residue. The fermentability of RS was estimated from the faecal recovery of starch in normal animals with intact hind‐gut microflora. Approximately 35 g per 100 g and 32 g per 100 g were RS in the case of raw potato starch and the RS‐enriched preparation, respectively, versus only 1 g per 100 g in the case of raw pea starch. The caecal pH decreased with all test diets, being most significant with raw potato starch. SCFA production and faecal bulking were negligible with raw pea starch, whereas both raw potato starch and the RS‐enriched preparation significantly increased these parameters. The fermentability of RS in raw potato starch and the RS‐enriched preparation was similar, or about 60–70%. If calculated on basis of fermented amount, RS in raw potato starch was more potent in generating SCFA (49 μmol g−1) than in the RS‐enriched preparation (19 μmol g−1). RS in raw potato starch also displayed the highest faecal bulking capacity. In fact, the faecal dry weight increased more than expected merely from delivery of RS. The relative proportion in caecal contents of acetic‐, propionic‐ and butyric acid was 70, 17 and 8%, respectively, with no significant differences between the three sources of RS.
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| 7. |
- Björck, Svante, et al.
(författare)
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A South Atlantic island record uncovers shifts in westerlies and hydroclimate during the last glacial
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:6, s. 1939-1958
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the latitudinal position and strength of the Southern Hemisphere westerlies (SHW) are thought to be tightly coupled to important climate processes, such as cross-equatorial heat fluxes, Atlantic Meridional Overturning Circulation (AMOC), the bipolar seesaw, Southern Ocean ventilation and atmospheric CO2 levels. However, many uncertainties regarding magnitude, direction, and causes and effects of past SHW shifts still exist due to lack of suitable sites and scarcity of information on SHW dynamics, especially from the last glacial. Here we present a detailed hydroclimate multiproxy record from a 36.4-18.6 kyr old lake sediment sequence on Nightingale Island (NI). It is strategically located at 37ĝF S in the central South Atlantic (SA) within the SHW belt and situated just north of the marine Subtropical Front (SF). This has enabled us to assess hydroclimate changes and their link to the regional climate development as well as to large-scale climate events in polar ice cores. The NI record exhibits a continuous impact of the SHW, recording shifts in both position and strength, and between 36 and 31 ka the westerlies show high latitudinal and strength-wise variability possibly linked to the bipolar seesaw. This was followed by 4 kyr of slightly falling temperatures, decreasing humidity and fairly southerly westerlies. After 27 ka temperatures decreased 3-4 ĝC, marking the largest hydroclimate change with drier conditions and a variable SHW position. We note that periods with more intense and southerly-positioned SHW seem to be related to periods of increased CO2 outgassing from the ocean, while changes in the cross-equatorial gradient during large northern temperature changes appear as the driving mechanism for the SHW shifts. Together with coeval shifts of the South Pacific westerlies, our results show that most of the Southern Hemisphere experienced simultaneous atmospheric circulation changes during the latter part of the last glacial. Finally we can conclude that multiproxy lake records from oceanic islands have the potential to record atmospheric variability coupled to large-scale climate shifts over vast oceanic areas..
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| 8. |
- Blaak, E E, et al.
(författare)
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Impact of postprandial glycaemia on health and prevention of disease.
- 2012
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Ingår i: Obesity Reviews. - 1467-7881. ; 13:10, s. 923-984
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Tidskriftsartikel (refereegranskat)abstract
- Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise perfomance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal-related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia.
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