J Pediatr Genet 2021; 10(02): 098-104
DOI: 10.1055/s-0040-1714697
Original Article

Polymorphism of Proteasomal Genes Can Be a Risk Factor for Systemic Autoimmune Diseases in Children

1   Laboratory of Molecular Basis of Genome Stability, Institute of Genetics and Cytology, National Academy of Sciences of Belarus, Minsk, Republic of Belarus
,
1   Laboratory of Molecular Basis of Genome Stability, Institute of Genetics and Cytology, National Academy of Sciences of Belarus, Minsk, Republic of Belarus
,
Natalia V. Nikitchenko
1   Laboratory of Molecular Basis of Genome Stability, Institute of Genetics and Cytology, National Academy of Sciences of Belarus, Minsk, Republic of Belarus
,
Elena V. Sechko
2   1st Department of Childhood Diseases, Belarusian State Medical University, Minsk, Republic of Belarus
,
Alexej M. Tchitchko
2   1st Department of Childhood Diseases, Belarusian State Medical University, Minsk, Republic of Belarus
,
Galina M. Batyan
2   1st Department of Childhood Diseases, Belarusian State Medical University, Minsk, Republic of Belarus
,
Alexander V. Sukalo
2   1st Department of Childhood Diseases, Belarusian State Medical University, Minsk, Republic of Belarus
,
1   Laboratory of Molecular Basis of Genome Stability, Institute of Genetics and Cytology, National Academy of Sciences of Belarus, Minsk, Republic of Belarus
› Author Affiliations

Abstract

The study aimed to assess the involvement of three proteasomal genes, PSMA6, PSMC6, and PSMA3, in autoimmune pathogenesis by analyzing associations between single nucleotide polymorphisms and systemic rheumatic diseases with a different autoimmune component: juvenile idiopathic arthritis (JIA), the juvenile form of systemic lupus erythematosus, and Kawasaki's disease (KD). Our results showed that the PSMA6 (rs1048990) polymorphism can be a risk factor for JIA (false discovery rate q ≤ 0.090), while PSMA3 (rs2348071) has a tendency to be nonspecific and is shared with JIA and other autoimmune diseases, including KD, an illness with very low autoimmune activity and high autoinflammation.

Note

This work was carried out in the framework of the project “Molecular genetic assessment of autoimmune diseases risk” as part of the Research Technical Program “DNA identification” (2017–2021).




Publication History

Received: 15 April 2020

Accepted: 10 June 2020

Article published online:
04 August 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Kammerl IE, Meiners S. Proteasome function shapes innate and adaptive immune responses. Am J Physiol Lung Cell Mol Physiol 2016; 311 (02) L328-L336
  • 2 Gomes AV. Genetics of proteasome diseases. Scientifica (Cairo) 2013; 2013: 1-30
  • 3 Chen ZJ. Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol 2005; 7 (08) 758-765
  • 4 Liu Q, Chen Y, Auger-Messier M, Molkentin JD. Interaction between NFκB and NFAT coordinates cardiac hypertrophy and pathological remodeling. Circ Res 2012; 110 (08) 1077-1086
  • 5 Brehm A, Liu Y, Sheikh A. et al. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest 2015; 125 (11) 4196-4211
  • 6 Zemeckienė Z, Vitkauskienė A, Sjakste T, Sitkauskienė B, Sakalauskas R. Proteasomes and proteasomal gene polymorphism in association with inflammation and various diseases. Medicina (Kaunas) 2013; 49 (05) 207-213
  • 7 Sjakste T, Paramonova N, Rumba-Rozenfelde I, Trapina I, Sugoka O, Sjakste N. Juvenile idiopathic arthritis subtype- and sex-specific associations with genetic variants in the PSMA6/PSMC6/PSMA3 gene cluster. Pediatr Neonatol 2014; 55 (05) 393-403
  • 8 Wang J, Maldonado MA. The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. Cell Mol Immunol 2006; 3 (04) 255-261
  • 9 Thierry S, Fautrel B, Lemelle I, Guillemin F. Prevalence and incidence of juvenile idiopathic arthritis: a systematic review. Joint Bone Spine 2014; 81 (02) 112-117
  • 10 Levy DM, Kamphuis S. Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am 2012; 59 (02) 345-364
  • 11 Hall GC, Tulloh LE, Tulloh RMR. Kawasaki disease incidence in children and adolescents: an observational study in primary care. Br J Gen Pract 2016; 66 (645) e271-e276
  • 12 Ozaki K, Sato H, Iida A. et al. A functional SNP in PSMA6 confers risk of myocardial infarction in the Japanese population. Nat Genet 2006; 38 (08) 921-925
  • 13 Wang H, Jiang M, Zhu H. et al. Quantitative assessment of the influence of PSMA6 variant (rs1048990) on coronary artery disease risk. Mol Biol Rep 2013; 40 (02) 1035-1041
  • 14 Xu H, Han H, Song S. et al. Exosome-transmitted PSMA3 and PSMA3–AS1 promote proteasome inhibitor resistance in multiple myeloma. Clin Cancer Res 2019; 25 (06) 1923-1935
  • 15 Petty RE, Southwood TR, Manners P. et al; International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004; 31 (02) 390-392
  • 16 Aringer M, Costenbader K, Daikh D. et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019; 78 (09) 1151-1159
  • 17 Demirkaya E, Sahin S, Romano M, Zhou Q, Aksentijevich I. New horizons in the genetic etiology of systemic lupus erythematosus and lupus-like disease: monogenic lupus and beyond. J Clin Med 2020; 9 (03) 712
  • 18 McCrindle BW, Rowley AH, Newburger JW. et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation 2017; 135 (17) e927-e999
  • 19 Sambrook J, Russell DW. Isolation of high-molecular-weight DNA from mammalian cells using proteinase K and phenol. CSH Protoc 2006; 2006 (01) pdb.prot4036
  • 20 González JR, Armengol L, Solé X. et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics 2007; 23 (05) 644-645
  • 21 Moore JH, Gilbert JC, Tsai C-T. et al. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J Theor Biol 2006; 241 (02) 252-261
  • 22 Storey JD. A direct approach to false discovery rates. J R Stat Soc Series B Stat Methodol 2002; 64 (03) 479-498
  • 23 Sudmant PH, Rausch T, Gardner EJ. et al; 1000 Genomes Project Consortium. An integrated map of structural variation in 2,504 human genomes. Nature 2015; 526 (7571): 75-81
  • 24 Sjakste T, Paramonova N, Wu LS-S. et al. PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity in Latvians, Lithuanians and Taiwanese. Meta Gene 2014; 2: 283-298
  • 25 Sherry ST, Ward MH, Kholodov M. et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001; 29 (01) 308-311
  • 26 McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006; 3 (08) e297
  • 27 Zhang W, Wei Q. Calcineurin stimulates the expression of inflammatory factors in RAW 264.7 cells by interacting with proteasome subunit alpha type 6. Biochem Biophys Res Commun 2011; 407 (04) 668-673
  • 28 Zhang Y, Lingappan K. Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells. Biochem Biophys Res Commun 2017; 486 (02) 431-437
  • 29 Wilhelm CJ, Hashimoto JG, Roberts ML, Sonmez MK, Wiren KM. Understanding the addiction cycle: a complex biology with distinct contributions of genotype vs. sex at each stage. Neuroscience 2014; 279: 168-186
  • 30 Lonsdale J, Thomas J, Salvatore M. et al; GTEx Consortium. The genotype-tissue expression (GTEx) project. Nat Genet 2013; 45 (06) 580-585
  • 31 Qiu B-Q, Lin X-H, Ye X-D. et al. Long non-coding RNA PSMA3-AS1 promotes malignant phenotypes of esophageal cancer by modulating the miR-101/EZH2 axis as a ceRNA. Aging (Albany NY) 2020; 12 (02) 1843-1856