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HLA class I genes m...
HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes
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- Jiang, Ziyu (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Ren, Wenqian (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Liang, Hua (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Yan, Jinhua (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Yang, Daizhi (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Luo, Sihui (författare)
- University of Science and Technology of China,Third Affiliated Hospital of Sun Yat‐sen University
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- Zheng, Xueying (författare)
- Third Affiliated Hospital of Sun Yat‐sen University,University of Science and Technology of China
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- Lin, Guo Wang (författare)
- Sun Yat-sen University
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- Xian, Yingxin (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Xu, Wen (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Yao, Bin (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Noble, Janelle A. (författare)
- Children's Hospital Oakland Research Institute
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- Bei, Jin Xin (författare)
- Sun Yat-sen University
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- Groop, Leif (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Weng, Jianping (författare)
- University of Science and Technology of China,Third Affiliated Hospital of Sun Yat‐sen University
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(creator_code:org_t)
- 2021-05-22
- 2021
- Engelska.
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64:9, s. 2026-2036
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http://dx.doi.org/10... (free)
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https://link.springe...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Aims/hypothesis: The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes. Methods: A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing. Results: The susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. Conclusions/interpretation: In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies. Graphical abstract: [Figure not available: see fulltext.].
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Basic science
- Genetics of type 1 diabetes
- Human
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Jiang, Ziyu
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Ren, Wenqian
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Liang, Hua
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Yan, Jinhua
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Yang, Daizhi
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Luo, Sihui
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Zheng, Xueying
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Lin, Guo Wang
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Xian, Yingxin
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Xu, Wen
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Yao, Bin
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Noble, Janelle A ...
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Bei, Jin Xin
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Groop, Leif
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Weng, Jianping
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