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  • Ning, YujieKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)

Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-01-11
  • Frontiers Media S.A.2022
  • electronicrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:umu-192028
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-192028URI
  • https://doi.org/10.3389/fgene.2021.773534DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • The mechanism of environmental factors in Kashin-Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin-responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin-responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.

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  • Hu, MinhanKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Diao, JiayuShaanxi Provincial People's Hospital, Xi'an, China (author)
  • Gong, YiKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Huang, RuitianKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Chen, SijieKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Zhang, FeiyuKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Liu, YanliKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Chen, FeihongKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Zhang, PanKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Zhao, GuanghuiXi'an Honghui Hospital, Xi'an, China (author)
  • Chang, YanhaiShaanxi Provincial People's Hospital, Xi'an, China (author)
  • Xu, KeXi'an Honghui Hospital, Xi'an, China (author)
  • Zhou, RongKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China; Shaanxi Provincial Institute for Endemic Disease Control, Xi'an, China (author)
  • Li, ChengKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China; Shaanxi Provincial Institute for Endemic Disease Control, Xi'an, China (author)
  • Zhang, FengKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Lammi, Mikko,1961-Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Key Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China,Chondrogenic and osteogenic differentiation(Swepub:umu)mila0077 (author)
  • Wang, XiKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Guo, XiongKey Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China (author)
  • Key Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, ChinaShaanxi Provincial People's Hospital, Xi'an, China (creator_code:org_t)

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  • In:Frontiers in Genetics: Frontiers Media S.A.121664-8021

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