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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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| 2. |
- Sun, Chengjun, et al.
(författare)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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| 4. |
- Nilsson, Mimmi K. M., et al.
(författare)
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Precise U-Pb baddeleyite ages of mafic dykes and intrusions in southern West Greenland and implications for a possible reconstruction with the Superior craton
- 2010
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Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268. ; 183:3, s. 399-415
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Tidskriftsartikel (refereegranskat)abstract
- The Archaean block of southern Greenland constitutes the core of the North Atlantic craton (NAC) and is host to a large number of Precambrian mafic intrusions and dyke swarms, many of which are regionally extensive but poorly dated. For southern West Greenland, we present a U-Pb zircon age of 2990 +/- 13 Ma for the Amikoq mafic-ultramafic layered intrusion (Fiskefjord area) and four baddeleyite U-Pb ages of Precambrian dolerite dykes. Specifically, a dyke located SE of Ameralik Fjord is dated at 2499 +/- 2 Ma, similar to a previously reported Ar-40/Ar-39 age of a dyke in the Kangamiut area. For these and related intrusions of ca. 2.5 Ga age in southern West Greenland, we propose the name Kilaarsarfik dykes. Three WNW-trending dykes of the MD3 swarm yield ages of 2050 +/- 2 Ma, 2041 +/- 3 Ma and 2029 +/- 3 Ma. A similar U-Pb baddeleyite age of 2045 +/- 2 Ma is also presented for a SE-trending dolerite (Iglusuataliksuak dyke) in the Nain Province, the rifted western block of the NAC in Labrador. We speculate that the MD3 dykes and age-equivalent NNE-trending Kangamiut dykes of southern West Greenland, together with the Iglusuataliksuak dyke (after closure of the Labrador Sea) represent components of a single, areally extensive, radiating swarm that signaled the arrival of a mantle plume centred on what is presently the western margin of the North Atlantic craton. Comparison of the magmatic 'barcodes' from the Nain and Greenland portions of the North Atlantic craton with the established record from the north-eastern Superior craton shows matches at 2500 Ma, 2214 Ma, 2050-2030 Ma and 1960-1950 Ma. We use these new age constraints, together with orientations of the dyke swarms, to offer a preliminary reconstruction of the North Atlantic craton near the north-eastern margin of the Superior craton during the latest Archaean and early Palaeoproterozoic, possibly with the Core Zone craton of eastern Canada intervening. (C) 2010 Elsevier B.V. All rights reserved.
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