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  • Jiang, ZiyuThird Affiliated Hospital of Sun Yat‐sen University (author)

HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-05-22
  • Springer Science and Business Media LLC,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:43b40154-2165-4417-a85f-e3a27e8f46ed
  • https://lup.lub.lu.se/record/43b40154-2165-4417-a85f-e3a27e8f46edURI
  • https://doi.org/10.1007/s00125-021-05476-6DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.].

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  • Ren, WenqianThird Affiliated Hospital of Sun Yat‐sen University (author)
  • Liang, HuaThird Affiliated Hospital of Sun Yat‐sen University (author)
  • Yan, JinhuaThird Affiliated Hospital of Sun Yat‐sen University (author)
  • Yang, DaizhiThird Affiliated Hospital of Sun Yat‐sen University (author)
  • Luo, SihuiUniversity of Science and Technology of China,Third Affiliated Hospital of Sun Yat‐sen University (author)
  • Zheng, XueyingThird Affiliated Hospital of Sun Yat‐sen University,University of Science and Technology of China (author)
  • Lin, Guo WangSun Yat-sen University (author)
  • Xian, YingxinThird Affiliated Hospital of Sun Yat‐sen University (author)
  • Xu, WenThird Affiliated Hospital of Sun Yat‐sen University(Swepub:lu)we3714xu (author)
  • Yao, BinThird Affiliated Hospital of Sun Yat‐sen University (author)
  • Noble, Janelle A.Children's Hospital Oakland Research Institute (author)
  • Bei, Jin XinSun Yat-sen University (author)
  • Groop, LeifLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)endo-lgr (author)
  • Weng, JianpingUniversity of Science and Technology of China,Third Affiliated Hospital of Sun Yat‐sen University (author)
  • Third Affiliated Hospital of Sun Yat‐sen UniversityUniversity of Science and Technology of China (creator_code:org_t)

Related titles

  • In:Diabetologia: Springer Science and Business Media LLC64:9, s. 2026-20360012-186X1432-0428

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