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- Arnheim, L, et al.
(författare)
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A population-based cohort study of KIR genes and genotypes in relation to cervical intraepithelial neoplasia
- 2005
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Ingår i: Tissue Antigens. - Copenhagen : Blackwell Munksgaard. - 0001-2815 .- 1399-0039. ; 65:3, s. 252-259
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells are involved both in control of virus infections and in elimination of tumor cells. Killer immunoglobulin-like receptors (KIRs) either activate or inhibit NK cell-mediated cytolysis, protecting healthy cells from destruction while enabling killing of abnormal cells. To investigate whether KIR genes or genotypes are associated with cervical carcinogenesis, a nested case-control study of 65 case women with cervical intraepithelial neoplasia (CIN) diagnosed during a 6-year follow-up of 15,234 women and 150 control women from the same cohort that remained healthy was performed. More than 70 different genotypes were observed, and 33 of which had not been described previously. An A-genotype including KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, KIR3DL3, and KIR2DS4 was associated with increased risk of CIN (OR 6.7; 95% CI 1.7-26.3), and KIR2DL5B*002 appeared to have an inverse association with disease (OR 0.5; 95% CI 0.5-2.9). There was no association of CIN with the number of activating KIR genes. There was also no association between KIR genes and type of human papilloma virus or with other CIN-related immune response genes. It was concluded that certain KIR genes and genotypes may associate with cervical neoplasia.
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- Berzina, L, et al.
(författare)
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Newborn screening for high-risk human leukocyte antigen markers associated with insulin-dependent diabetes mellitus : The ABIS study
- 2002
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Ingår i: Annals of the New York Academy of Sciences. - 0077-8923 .- 1749-6632. ; 958, s. 312-316
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 (insulin-dependent) diabetes mellitus is associated with specific high-risk HLA DQ and DR haplotypes and islet cell antibodies. IDDM susceptibility in Caucasians is more strongly associated with DQ2/DQ8 (DQA1*0501-DQB1*0201/DQA1*0301-DQB1*0302) and DQ6 (B1*0604) than with DRB1*03/DRB1*04, while a single copy of DQ6 (B1*0602) gives sufficient protection against type 1 diabetes. As a part of the ABIS (All Babies in Southeast Sweden) study we have done typing of DQA1, DQB1, and DRB1 by polymerase chain reaction (PCR) amplification of the second exon of the genes, manually dot-blotting onto nylon membranes synthetic sequence-specific oligonucleotide (SSO) probes, 3' end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography using the SSO probe. Among 3756 newborns born in southeast Sweden we have found the high-risk genotype DQ2/DR3-DO8/DR4 to be present in 1%, haplotype DQ8/DR4 in 7.8%, and haplotype DQ2/DR3 in 9.6%. DQ2/DR3 or DQ8/DR4 was carried by 16.4% of newborns, the low-risk DQ6 molecule was carried by newborns as follows: DQ2/DR3-DQ6/DR15, 1.3%, DQ8/DR4-DQ6/DR15, 1.3%, and DQ6/DR15, 9.4%. We conclude from our results that the high incidence of IDDM in Sweden is at least in part due to increased prevalence of high-risk HLA haplotypes compared to protective haplotypes (20% vs. 13%) in the general population.
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- Graham, J, et al.
(författare)
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Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:5, s. 1346-1355
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Tidskriftsartikel (refereegranskat)abstract
- Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0–34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3′ end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.
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- Gupta, M, et al.
(författare)
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Coxsackie virus B antibodies are increased in HLA DR3-MICA5.1 positive type 1 diabetes patients in the Linkoping region of Sweden
- 2003
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Ingår i: Human Immunology. - 0198-8859. ; 64:9, s. 874-879
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which genetics and environmental factors play a role. Among the environmental factors, viruses (especially Coxsackie virus B [CBV]), and among genetic markers, human leukocyte antigen (HLA) DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) and DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2), and major histocompatibility complex class I chain-related gene-A (MICA) alleles 5 and 5.1 have been reported to be associated with T1DM in Caucasians. Sweden ranks third in the world for T1DM incidence. In Sweden, the Linkoping region indicates the highest incidence for T1DM. In this study, we analyzed whether antibodies against CBV are increased in DR3, DR4, MICA5, or MICA5.1 positive patients from Linkoping (n = 46) and from Swedish population as a whole (n = 298) between the age of 0 and 15 years old. There was no difference in the frequency of antibodies to CBV in patients compared with controls in Linkoping (26% vs 23%) or in all of Sweden (26% vs 21%). However, CBV antibodies were increased in DR3, DR3-DR4 (heterozygous), DR3-MICA5.1, and DR3-DR4-MICA5.1 positive compared with DR3, DR3-DR4, DR3-MICA5.1, and DR3-DR4-MICA5.1 negative patients in Linkoping (p < 0.05 for all), but not in Swedish population as a whole. Thus, our study suggests that in addition to DR3, MICA5.1 has an influence on the immune response to CBV infection in patients from Linkoping. (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Inc.
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- Gupta, M, et al.
(författare)
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Frequency of MICA in all babies in southeast Sweden (ABIS) positive for high-risk HLA-DQ associated with type 1 diabetes
- 2004
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1037, s. 138-144
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes mellitus (T1DM) is an autoimmune disease known to occur in genetically susceptible individuals after exposure to certain unknown environmental factors. HLA-DR3-DQ2 or DR4-DQ8 are established genetic markers for the disease. MHC class I chain-related gene-A (MICA) gene polymorphism has been proposed to be associated with T1DM. To identify the environmental factors and for implementing intervention trials to prevent T1DM, it is important to screen subjects at genetically increased risk for developing T1DM. The All Babies in Southeast Sweden (ABIS) study aims to assess the risk of future progression to T1DM in the general child population. In the present report, we studied the frequency of MICA alleles among newborn babies carrying high-risk HLA DQ2 or DQ8. Of 2821 newborns, we found 563 subjects positive for DQ2, 583 subjects positive for DQ8, 133 subjects positive for DQ2-DQ8 (heterozygous), and 1013 subjects positive for either DQ2 or DQ8. Of these 1013 babies, we typed 499 babies for MICA. Frequency of MICA5 was 38% among DQ8+9 35% among for DQ2-DQ8 (heterozygous) positives, and 22.5% among DQ2+ babies. Frequency of MICA5.1 was 81% among DQ+, 62% among DQ8+, and 71% among DQ2.-DQ8 (heterozygous) positives. Frequency of MICA6 was between 20% and 22% among the three groups. Frequency of MICA5/5.1 was 19% among DQ2-DQ8 (heterozygous) positives and between 12% and 13% among those positive for DQ2, DQ89 DQ2, or DQ8. The results from genetic typing in this study would be useful, in conjunction with results from autoantibody analysis that are prospectively being followed-up in all the babies, to develop an approach for identifying children at risk for developing T1DM. Inclusion of MICA typing in addition to HLA could be useful for screening of genetic markers associated with T1DM.
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