TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus (original) (raw)

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.

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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

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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).

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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
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  2. Yoon-Kyoung Sung
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  3. Hyoung Doo Shin
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  4. Byung Lae Park
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  5. Hyun Sub Cheong
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  6. Sang-Cheol Bae
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Correspondence toSang-Cheol Bae.

Additional information

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

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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

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