Skip to main content

Advertisement

SpringerLink
Log in

A study on associations of single-nucleotide polymorphisms within H19 and HOX transcript antisense RNA (HOTAIR) with genetic susceptibility to rheumatoid arthritis in a Chinese population

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

The purpose of our study was to examine whether the H19 rs2839698, rs217727, and HOX transcript antisense RNA (HOTAIR) rs12826786 polymorphisms were associated with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population.

Methods

A total of 777 participants were enrolled in this study, including 328 RA patients and 449 healthy controls. The H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms were detected by the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology.

Results

No significant difference in genotype distribution between RA patients and healthy controls was found (P = 0.38 for rs2839698; P = 0.79 for rs217727; P = 0.39 for rs12826786). The difference in allele frequencies between RA patients and controls was also non-significant (rs2839698 T versus C, P = 0.23, odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.92–1.43; rs217727 C versus T, P = 0.55, OR = 1.07, 95% CI = 0.87–1.32; and rs12826786 T versus C, P = 0.32, OR = 1.14, 95% CI = 0.88–1.47). We have also evaluated the relationships of above-mentioned polymorphisms with risk of RA under dominant model and recessive model, but non-significant evidence was found. No significant evidence was detected for the relationships of H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms with risk of different serotypes of RA.

Conclusions

Our results indicated that H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms might not be involved in the genetic background of RA in Chinese.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–19.

    Article  CAS  PubMed  Google Scholar 

  2. Li R, Sun J, Ren LM, Wang HY, Liu WH, Zhang XW, et al. Epidemiology of eight common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing. Rheumatology (Oxford). 2012;51(4):721–9.

    Article  Google Scholar 

  3. Terao C, Ikari K, Nakayamada S, Takahashi Y, Yamada R, Ohmura K, et al. A twin study of rheumatoid arthritis in the Japanese population. Mod Rheumatol. 2016;26(5):685–9.

    Article  PubMed  Google Scholar 

  4. Silman AJ, MacGregor AJ, Thomson W, Holligan S, Carthy D, Farhan A, et al. Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br J Rheumatol. 1993;32(10):903–7.

    Article  CAS  PubMed  Google Scholar 

  5. Bellamy N, Duffy D, Martin N, Mathews J. Rheumatoid arthritis in twins: a study of aetiopathogenesis based on the Australian Twin Registry. Ann Rheum Dis. 1992;51(5):588–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Frisell T, Holmqvist M, Källberg H, Klareskog L, Alfredsson L, Askling J. Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 2013;65(11):2773–82.

    Article  CAS  PubMed  Google Scholar 

  7. Hemminki K, Li X, Sundquist J, Sundquist K. Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions. Arthritis Rheum. 2009;60(3):661–8.

    Article  PubMed  Google Scholar 

  8. Grant SF, Thorleifsson G, Frigge ML, Thorsteinsson J, Gunnlaugsdóttir B, Geirsson AJ, et al. The inheritance of rheumatoid arthritis in Iceland. Arthritis Rheum. 2001;44(10):2247–54.

    Article  CAS  PubMed  Google Scholar 

  9. del Junco D, Luthra HS, Annegers JF, Worthington JW, Kurland LT. The familial aggregation of rheumatoid arthritis and its relationship to the HLA-DR4 association. Am J Epidemiol. 1984;119(5):813–29.

    Article  PubMed  Google Scholar 

  10. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506(7488):376–81.

    Article  CAS  PubMed  Google Scholar 

  11. Ding J, Eyre S, Worthington J. Genetics of RA susceptibility, what comes next? RMD Open. 2015;1(1):e000028.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Erdmann VA, Szymanski M, Hochberg A, Groot N, Barciszewski J. Non-coding, mRNA-like RNAs database Y2K. Nucleic Acids Res. 2000;28(1):197–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.

    Article  CAS  PubMed  Google Scholar 

  14. Stuhlmüller B, Kunisch E, Franz J, Martinez-Gamboa L, Hernandez MM, Pruss A, et al. Detection of oncofetal h19 RNA in rheumatoid arthritis synovial tissue. Am J Pathol. 2003;163(3):901–11.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Song J, Kim D, Han J, Kim Y, Lee M, Jin EJ. PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med. 2015;15(1):121–6.

    Article  CAS  PubMed  Google Scholar 

  16. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129(7):1311–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Raveh E, Matouk IJ, Gilon M, Hochberg A. The H19 Long non-coding RNA in cancer initiation, progression and metastasis - a proposed unifying theory. Mol Cancer. 2015;14:184.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hajjari M, Salavaty A. HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med. 2015;12(1):1–9.

    PubMed  PubMed Central  Google Scholar 

  19. Verhaegh GW, Verkleij L, Vermeulen SH, den Heijer M, Witjes JA, Kiemeney LA. Polymorphisms in the H19 gene and the risk of bladder cancer. Eur Urol. 2008;54(5):1118–26.

    Article  CAS  PubMed  Google Scholar 

  20. Yang C, Tang R, Ma X, Wang Y, Luo D, Xu Z, et al. Tag SNPs in long non-coding RNA H19 contribute to susceptibility to gastric cancer in the Chinese Han population. Oncotarget. 2015;6(17):15311–20.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Li S, Hua Y, Jin J, Wang H, Du M, Zhu L, et al. Association of genetic variants in lncRNA H19 with risk of colorectal cancer in a Chinese population. Oncotarget. 2016;7(18):25470–7.

    PubMed  PubMed Central  Google Scholar 

  22. Xia Z, Yan R, Duan F, Song C, Wang P, Wang K. Genetic polymorphisms in long noncoding RNA H19 are associated with susceptibility to breast cancer in Chinese population. Medicine (Baltimore). 2016;95(7):e2771.

    Article  CAS  Google Scholar 

  23. Hua Q, Lv X, Gu X, Chen Y, Chu H, Du M, et al. Genetic variants in lncRNA H19 are associated with the risk of bladder cancer in a Chinese population. Mutagenesis. 2016;31(5):531–8.

    Article  CAS  PubMed  Google Scholar 

  24. Guo W, Dong Z, Bai Y, Guo Y, Shen S, Kuang G, et al. Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumour Biol. 2015;36(4):2845–54.

    Article  CAS  PubMed  Google Scholar 

  25. Bayram S, Sümbül AT, Dadaş E. A functional HOTAIR rs12826786 C > T polymorphism is associated with breast cancer susceptibility and poor clinicopathological characteristics in a Turkish population: a hospital-based case-control study. Tumour Biol. 2016;37(4):5577–84.

    Article  CAS  PubMed  Google Scholar 

  26. Ohmura K, Terao C, Maruya E, Katayama M, Matoba K, Shimada K, et al. Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset: a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis. Rheumatology (Oxford). 2010;49(12):2298–304.

    Article  CAS  Google Scholar 

  27. Viatte S, Plant D, Bowes J, Lunt M, Eyre S, Barton A, et al. Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated peptide antibody negative patients. Ann Rheum Dis. 2012;71(12):1984–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Han B, Diogo D, Eyre S, Kallberg H, Zhernakova A, Bowes J, et al. Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. Am J Hum Genet. 2014;94(4):522–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Viatte S, Massey J, Bowes J, Duffus K, arcOGEN Consortium, Eyre S, et al. Replication of associations of genetic loci outside the HLA region with susceptibility to anti-cyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheumatol. 2016;68(7):1603–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315–24.

    Article  CAS  PubMed  Google Scholar 

  31. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–2581.

    Article  PubMed  Google Scholar 

  32. Brannan CI, Dees EC, Ingram RS, Tilghman SM. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990;10(1):28–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gabory A, Jammes H, Dandolo L. The H19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays. 2010;32(6):473–80.

    Article  CAS  PubMed  Google Scholar 

  34. Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G, et al. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol. 2012;14(7):659–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, et al. The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell. 2013;52(1):101–12.

    Article  CAS  PubMed  Google Scholar 

  36. Xia T, Liao Q, Jiang X, Shao Y, Xiao B, Xi Y, et al. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep. 2014;4:6088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Matouk IJ, Halle D, Raveh E, Gilon M, Sorin V, Hochberg A. The role of the oncofetal H19 lncRNA in tumor metastasis: orchestrating the EMT-MET decision. Oncotarget. 2016;7(4):3748–65.

    PubMed  Google Scholar 

  38. Wang WT, Ye H, Wei PP, Han BW, He B, Chen ZH, et al. LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner. J Hematol Oncol. 2016;9(1):117.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329(5992):689–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ma MZ, Li CX, Zhang Y, Weng MZ, Zhang MD, Qin YY, et al. Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer. 2014;13:156.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by National Natural Science Foundation of China (Grant No. 81602921), Nature Science Foundation of Ningbo city (Grant No. 2015A610205), Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University Talent Project (Grant No. 421504530), School Research Foundation of Ningbo University (Grant No. XKL14D2094), Ningbo Scientific Innovation Team for Environmental Hazardous Factor Control and Prevention (Grant No. 2016C51001), and K.C. Wong Magna Fund in Ningbo University.

Author information

Author notes

    Authors and Affiliations

    1. Department of Preventive Medicine, School of Medicine, Ningbo University, 818 Fenghua Road, 315211, Ningbo, Zhejiang, People’s Republic of China

      Jian-Zhe Zhou, Jing-Jing Li, Dong-Jin Hua, Si-Chao Huang, Qing-Qing Sun & Han Cen

    2. Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, 315211, Ningbo, Zhejiang, People’s Republic of China

      Jian-Zhe Zhou, Jing-Jing Li, Dong-Jin Hua, Si-Chao Huang, Qing-Qing Sun & Han Cen

    3. Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, 59 Liuting Road, 315010, Ningbo, Zhejiang, People’s Republic of China

      Hua Huang & Xia-Fei Xin

    Authors
    1. Jian-Zhe Zhou
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jing-Jing Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Dong-Jin Hua
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Si-Chao Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Qing-Qing Sun
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Hua Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Xia-Fei Xin
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Han Cen
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Han Cen.

    Ethics declarations

    Conflict of interest

    The authors declare that there is no conflict of interest associated with this manuscript.

    Additional information

    Communicated by John Di Battista.

    J.-Z. Zhou, J.-J. Li and D.-J. Hua contributed equally to this work and should be considered as co-first author.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOCX 47 KB)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zhou, JZ., Li, JJ., Hua, DJ. et al. A study on associations of single-nucleotide polymorphisms within H19 and HOX transcript antisense RNA (HOTAIR) with genetic susceptibility to rheumatoid arthritis in a Chinese population. Inflamm. Res. 66, 515–521 (2017). https://doi.org/10.1007/s00011-017-1035-5

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00011-017-1035-5

    Keywords

    Search

    Navigation