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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Guo, JP, et al.
(författare)
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Sequencing of the MHC region defines HLA-DQA1 as the major genetic risk for seropositive rheumatoid arthritis in Han Chinese population
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:6, s. 773-780
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Tidskriftsartikel (refereegranskat)abstract
- The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (HLA)-DRB1. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC.MethodsWe first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case–control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants.ResultsHLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10−36, OR=2.29). DRβ1:37N had an independent protective effect (p=5.81×10−16, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRβ1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.ConclusionsWe provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405, is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.
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- Hu, CH, et al.
(författare)
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Visible-to-ultraviolet upconversion in Pr3+: Y2SiO5 crystals
- 2006
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Ingår i: Chemical Physics. - : Elsevier BV. - 0301-0104. ; 325:2, s. 563-566
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Tidskriftsartikel (refereegranskat)abstract
- The visible-to-ultraviolet upconversion in Pr3+:Y2SiO5 crystals have been investigated at room temperature for three different Pr3+ ion concentrations. The upconverted luminescence bands at the UV region from 270 to 350 nm were obtained with visible laser excitation. The upconversion mechanism was studied by observing the absorption and excitation spectra, the dependence of upconverted luminescence on pump power, and the decay profiles of the upconverted luminescence. It was found that the upconverted luminescence was produced by excited-state-absorption process using the P-3(J) and I-1(6) as intermediate states. (c) 2006 Elsevier B.V. All rights reserved.
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