Skip to main content
SpringerLink
Log in

TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

An Erratum to this article was published on 04 April 2008

Abstract

Three-prime repair exonucleases 1 and 2 (TREX1 and TREX2) play a role in the metabolism and clearance of DNA. The objective of this study was to confirm whether polymorphisms of TREX1 and TREX2 are associated with genetic susceptibility to systemic lupus erythematosus (SLE), and examine associations with autoantibodies (auto-Abs) in SLE. We investigated the genetic variants in 24 Korean individuals by direct sequencing. The genotype distributions of single-nucleotide polymorphisms (SNPs) and haplotypes were analyzed with multiple logistic regression models while controlling for covariates. We identified 12 and 5 SNPs of TREX1 and TREX2, of which −20260G>C, −389T>C, −381C>T, and +531C>T SNPs of TREX1; −23386G>C, −14703G>A, −7279C>T, and +1747C>T SNPs of TREX2; and each of three haplotypes were selected for larger scale genotyping (n = 1,053). No statistically significant association with the risk of SLE was observed in TREX1 and TREX2. TREX1 polymorphism −20260G>C showed protective effect on the production of anti-Ro Ab, and +531C>T in exon 16 and ht2 [G–T–C–T] showed also protective effect on the production of anti-dsDNA Ab, although the effect of +531C>T disappeared after multiple correction.

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

Fig. 1

Similar content being viewed by others

References

  1. Emlen W, Niebur J, Kadera R (1994) Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol 152:3685–3692

    PubMed  CAS  Google Scholar 

  2. Tan EM (1989) Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 44:93–151

    Article  PubMed  CAS  Google Scholar 

  3. Golan TD, Foltyn V, Roueff A (1991) Increased susceptibility to in vitro ultraviolet B radiation in fibroblasts and lymphocytes cultured from systemic lupus erythematosus patients. Clin Immunol Immunopathol 58:289–304

    Article  PubMed  CAS  Google Scholar 

  4. Rosenstein BS, Rosenstein RB, Zamansky GB (1992) Repair of DNA damage induced in systemic lupus erythematosus skin fibroblasts by simulated sunlight. J Invest Dermatol 98:469–474

    Article  PubMed  CAS  Google Scholar 

  5. Chitrabamrung S, Rubin RL, Tan EM (1981) Serum deoxyribonuclease I and clinical activity in systemic lupus erythematosus. Rheumatol Int 1:55–60

    Article  PubMed  CAS  Google Scholar 

  6. Tew MB, Johnson RW, Reveille JD, Tan FK (2001) A molecular analysis of the low serum deoxyribonuclease activity in lupus patients. Arthritis and Rheumatism 44:2446–2447

    Article  PubMed  CAS  Google Scholar 

  7. Mazur DJ, Perrino FW (1999) Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3′→5′ exonucleases. J Biol Chem 274:19655–19660

    Article  PubMed  CAS  Google Scholar 

  8. Morita M, Stamp G, Robins P, Dulic A, Rosewell I, Hrivnak G, Daly G, Lindahl T, Barnes DE (2004) Gene-targeted mice lacking the Trex1 (DNase III) 3′→5′ DNA exonuclease develop inflammatory myocarditis. Mol Cell Biol 24:6719–6727

    Article  PubMed  CAS  Google Scholar 

  9. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  PubMed  CAS  Google Scholar 

  10. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, Bacon P, Bombardieri S, Hanly J, Hay E, Isenberg D, Jones J, Kalunian K, Maddison P, Nived O, Petri M, Richter M, Sanchez-Guerrero J, Snaith M, Sturfelt G, Symmons D, Zoma A (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–369

    Article  PubMed  CAS  Google Scholar 

  11. Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 14:143–149

    PubMed  CAS  Google Scholar 

  12. Hedrick PW (1987) Gametic disequilibrium measures: proceed with caution. Genetics 117:331–341

    PubMed  CAS  Google Scholar 

  13. Hedrick P, Kumar S (2001) Mutation and linkage disequilibrium in human mtDNA. Eur J Hum Genet 9:969–972

    Article  PubMed  CAS  Google Scholar 

  14. Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989

    Article  PubMed  CAS  Google Scholar 

  15. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391:43–50

    Article  PubMed  CAS  Google Scholar 

  16. Wyllie AH (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556

    Article  PubMed  CAS  Google Scholar 

  17. Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz HG, Moroy T (2000) Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet 25:177–181

    Article  PubMed  CAS  Google Scholar 

  18. Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y (2001) Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet 28:313–314

    Article  PubMed  CAS  Google Scholar 

  19. Shin HD, Park BL, Kim LH, Lee HS, Kim TY, Bae SC (2004) Common DNase I polymorphism associated with autoantibody production among systemic lupus erythematosus patients. Hum Mol Genet 13:2343–2350

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partially supported by a grant of the Korea Health 21 R&D Project from the Ministry of Health and Welfare, Republic of Korea (no. 01-PJ3-PG6-01GN11-0002).

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Eulji University College of Medicine, Seoul, 139-711, Republic of Korea

    Jin-Wuk Hur

  2. Department of Internal Medicine, The Hospital for Rheumatic Diseases, Hanyang University Medical Center, 17 Haengdang-Dong, Seongdong-Gu, Seoul, 133-792, Republic of Korea

    Yoon-Kyoung Sung & Sang-Cheol Bae

  3. Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, 153-803, Republic of Korea

    Hyoung Doo Shin, Byung Lae Park & Hyun Sub Cheong

Authors
  1. Jin-Wuk Hur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoon-Kyoung Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyoung Doo Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Byung Lae Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyun Sub Cheong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sang-Cheol Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sang-Cheol Bae.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00296-008-0573-0

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hur, JW., Sung, YK., Shin, H.D. et al. TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus. Rheumatol Int 28, 783–789 (2008). https://doi.org/10.1007/s00296-007-0509-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-007-0509-0

Keywords

Search

Navigation