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Sökning: WFRF:(Scherstén B)

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1.
  • Shin, J-H, et al. (författare)
  • IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
  • 2007
  • Ingår i: Genes and Immunity. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-512
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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 <em>GIMAP5</em> 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) <em>rs6598</em>, located in a polyadenylation signal of <em>GIMAP5</em>, 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 <em>rs6598</em> had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected <em>P</em>=0.003), after adjusting for age at clinical onset (<em>P</em>=8.0 <img src="http://www.nature.com/__chars/math/special/times/black/med/base/glyph.gif" /> 10<sup>-13</sup>) and the numbers of HLA-DQ A1<sup>*</sup>0501-B1<sup>*</sup>0201 haplotypes (<em>P</em>=2.4 <img src="http://www.nature.com/__chars/math/special/times/black/med/base/glyph.gif" /> 10<sup>-5</sup>) and DQ A1<sup>*</sup>0301-B1<sup>*</sup>0302 haplotypes (<em>P</em>=0.002). <em>GIMAP5</em> 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 <em>GIMAP5</em> gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.</p>
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2.
  • Shin, J-H, et al. (författare)
  • IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.
  • 2007
  • Ingår i: Genes and Immunity. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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3.
  • Shin, JH, et al. (författare)
  • IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
  • 2007
  • Ingår i: Genes Immun. - 1466-4879 (Print). ; 8:6, s. 503-12
  • 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 times 10-13) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 times 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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4.
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5.
  • Graham, J, et al. (författare)
  • Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset
  • 1999
  • Ingår i: European Journal of Immunogenetics. - Wiley-Blackwell. - 0960-7420. ; 26:2-3, s. 117-127
  • Tidskriftsartikel (refereegranskat)abstract
    • HLA-associated relative risks of type 1 (insulin-dependent) diabetes mellitus were analysed in population-based Swedish patients and controls aged 0-34 years. The age dependence of HLA-associated relative risks was assessed by likelihood ratio tests of regression parameters in separate logistic regression models for each HLA category. The analyses demonstrated an attenuation with increasing age at onset in the relative risk for the positively associated DQB1*0201-A1*0502/B1*0302-A1*0301 (DQ2/8) genotype (P = 0.02) and the negatively associated DQB1*0602-A1*0102 (DQ6.2) haplotype (P = 0.004). At birth, DQ6.2-positive individuals had an estimated relative risk of 0.03, but this increased to 1.1 at age 35 years. Relative risks for individuals with DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ haplotype ether than 2, 8 or 6.2, were not significantly age-dependent. An exploratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that the risk of type 1 diabetes increases with age for DQB1*0604-A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301-A1*0501 haplotype is at age 18 years. There was also weak evidence that the risk for DQB1*0303-A1*0301 (DQ9), which has a positive association in the Japanese population, may decrease with age. We speculate that HLA-DQ alleles have a significant effect on the rate of beta cell destruction, which is accelerated in DQ2/8-positive individuals and inhibited, but not completely blocked, in DQ6.2-positive individuals.
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6.
  • Gyllenberg, Alexandra, et al. (författare)
  • Variability in the CIITA gene interacts with HLA in multiple sclerosis.
  • 2014
  • Ingår i: Genes and Immunity. - Nature Publishing Group. - 1476-5470. ; 15:3, s. 162-167
  • 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.
7.
  • Linjer, Erland, 1948-, et al. (författare)
  • Cost analysis of different pharmacological treatment strategies in elderly hypertensives.
  • 2005
  • Ingår i: Blood pressure. - 0803-7051. ; 14:2, s. 107-13
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:To compare costs for management of hypertension in elderly hypertensives randomized to starting treatment with conventional (beta-blockers/diuretics) therapy or a therapy initiated with a calcium antagonist or an angiotensin-converting enzyme (ACE) inhibitor. DESIGN: Health economic substudy in the Swedish Trial in Old Patients with Hypertension-2 (STOP Hypertension-2). SETTING:Outpatient clinics in Sweden. In this health economics substudy, 16/312 participating STOP-2 trial centers were selected. SUBJECTS: Elderly (70--84 years) patients (n=303) with a systolic and/or diastolic hypertension (or=180 and/or 105 mmHg). METHODS: Costs for patient management were analyzed and categorized in costs for routine care (protocol-driven costs, PDC), costs for extra visits or care (non-protocol-driven costs, NPDC), and direct drug costs (drug treatment costs, DTC). All calculations are related to costs during the first year of treatment after inclusion in STOP Hypertension-2. RESULTS: Out of the scheduled visits, a total of 99% were actually performed by the patients. There were no differences in the number of visits between the three treatment groups (diuretics/beta-blockers, calcium antagonists or ACE inhibitors). PDC did thus not differ between the three treatment groups. NPDC were similar in the conventional and calcium antagonist groups and lower than for the ACE inhibitor group. DTC were lower in the conventional treatment group compared with the other two groups. CONCLUSION. In elderly hypertensives in STOP Hypertension-2, total costs for management of hypertension were lower in patients assigned to diuretics, beta-blockers or calcium antagonists compared with ACE inhibitors during the first year of treatment. These results may be relevant to management of elderly hypertensive patients, especially in those patients without compelling indications or contraindications to starting treatment with either of these three main drug alternatives. Notably, with a specific drug regimen there are sizable NPDC such as extra visits and controls associated with symptoms or side-effects of a specific therapy, which significantly add to the total costs of treatment. Such costs, beyond the actual costs for the drugs, are important to realize and evaluate in order to provide the true costs for treatment of hypertensive patients.
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8.
  • Littorin, Bengt, et al. (författare)
  • Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS).
  • 2003
  • Ingår i: Journal of Internal Medicine. - Wiley-Blackwell Publishing Ltd. - 1365-2796. ; 254:3, s. 251-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study trends in body mass index (BMI) at diagnosis of diabetes in all young Swedish adults in the age range of 15-34 years registered in a nation-based registry. Design. The BMI was assessed at diagnosis in diabetic patients 15-34 years of age at diagnosis, for a period of 17 years (1983-1999). Islet cell antibodies (ICA) were measured during three periods (1987-1988, 1992-1993 and 1998-1999). Setting. A nationwide study (Diabetes Incidence Study in Sweden). Subjects. A total of 4727 type 1 and 1083 type 2 diabetic patients. Main outcome measures. Incidence-year specific BMI adjusted for age, gender and time of diagnosis (month). Results. Body mass index at diagnosis increased significantly both in type 1 (21.4 ± 3.6 to 22.5 ± 4.0; P < 0.0001) and in type 2 (27.4 ± 6.8 to 32.0 ± 6.0; P < 0.0001) diabetic patients, also when adjusted for age, gender and month of diagnosis. A similar significant increase in BMI was found in type 1 diabetic patients and in type 2 diabetic patients in the periods 1987-1988, 1992-1993 and 1998-1999; years when ICA were assessed and considered in the classification of diabetes. Despite this increase in BMI, there was no increase in the incidence of diabetes in young-adult people in Sweden. Conclusion. Body mass index at diagnosis of diabetes in subjects 15-34 years of age has substantially increased during 1983-1999 in Sweden when adjusted for age, gender and month of diagnosis.
9.
  • Sedimbi, S K, et al. (författare)
  • SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
  • 2007
  • Ingår i: Genes Immun. - 1466-4879 (Print). ; 8:6, s. 518-21
  • 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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10.
  • Sedimbi, S K, et al. (författare)
  • SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
  • 2007
  • Ingår i: Genes and Immunity. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-521
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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