Rheumatology International

, Volume 32, Issue 1, pp 91–96 | Cite as

Lack of association between Poly(ADP-ribose) polymerase (PARP) polymorphisms and rheumatoid arthritis in a Korean population

  • Kyeong-A Lee
  • So-Young Bang
  • Byung Lae Park
  • Jeong-Hyun Kim
  • Hyoung Doo Shin
  • Sang-Cheol BaeEmail author
Original Article


Several studies have investigated the roles of genetic polymorphisms in rheumatoid arthritis (RA). Some of these studies reported that polymorphisms of poly(ADP-ribose) polymerase 1 gene (PARP-1) are linked to rheumatoid arthritis. Poly(ADP-ribose) polymerase is an enzyme involved in DNA repair, genomic stability, apoptosis, gene transcription, proliferation, and autoimmunity. To determine whether genetic polymorphisms of PARP-1 are related to rheumatoid arthritis in a Korean population, six single nucleotide polymorphisms (SNPs), which were selected based on LDs and minor allele frequency (MAF > 0.05) in our previous study, were genotyped in 1,202 patients with rheumatoid arthritis and 979 unrelated healthy controls. As a result, no significant association between the susceptibility to rheumatoid arthritis and PAPR-1 polymorphisms was found. However, in further analysis depending on the radiological severity of rheumatoid arthritis, one PARP-1 polymorphism, rs1805413 (OR = 0.11; 95% CI = 0.02–0.55; P = 0.007; P corr = 0.04), and one haplotype (ht6, OR = 0.11; 95% CI = 0.02–0.55; P = 0.007; P corr = 0.04) were significantly associated with the radiological severity risk of RA in a recessive model. In addition, a recessive model revealed a correlation between one RA haplotype (ht4) and anti-CCP antibody negativity (OR 0.24, 95% CI 0.10–0.63, P = 0.003; P corr = 0.02). Despite a possible association between PARP-1 and the radiological severity of RA, this study found no statistical association between PARP-1 polymorphisms and the susceptibility to rheumatoid arthritis in a Korean population.


Rheumatoid arthritis (RA) Poly(ADP-ribose) polymerase (PARP) Polymorphism Susceptibility 



This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A010252).

Supplementary material

296_2010_1589_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 15 kb)


  1. 1.
    Stastny P (1978) Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 298:869–871PubMedCrossRefGoogle Scholar
  2. 2.
    Jawaheer D, Seldin MF, Amos CI, Chen WV, Shigeta R, Monteiro J, Kern M, Criswell LA, Albani S, Nelson JL, Clegg DO, Pope R, Schroeder HW Jr, Bridges SL Jr, Pisetsky DS, Ward R, Kastner DL, Wilder RL, Pincus T, Callahan LF, Flemming D, Wener MH, Gregersen PK (2001) A genomewide screen in multiplex rheumatoid arthritis families suggested genetic overlap with other autoimmune disease. Am J Hum Genet 68:927–936PubMedCrossRefGoogle Scholar
  3. 3.
    Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4 are associated with rheumatoid arthritis. Nat Genet 34:395–402PubMedCrossRefGoogle Scholar
  4. 4.
    Kang CP, Lee HS, Ju H, Cho H, Kang C, Bae SC (2006) A functional haplotype of the PADI4 gene associated with increased rheumatoid arthritis susceptibility in Koreans. Arthritis Rheum 54:90–96PubMedCrossRefGoogle Scholar
  5. 5.
    Cha S, Choi CB, Han TU, Kang CP, Kang C, Bae SC (2007) Association of anti-cyclic citrullinated peptide antibody levels with PADI4 haplotypes in early rheumatoid arthritis and with shared epitope alleles in very late rheumatoid arthritis. Arthritis Rheum 56:1454–1463PubMedCrossRefGoogle Scholar
  6. 6.
    Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith AM, Spoerke JM, Conn MT, Chang M, Chang SY, Saiki RK, Catanese JJ, Leong DU, Garcia VE, McAllister LB, Jeffery DA, Lee AT, Batliwalla F, Remmers E, Criswell LA, Seldin MF, Kastner DL, Amos CI, Sninsky JJ, Gregersen PK (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75:330–337PubMedCrossRefGoogle Scholar
  7. 7.
    Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, Liew A, Khalili H, Chandrasekaran A, Davies LR, Li W, Tan AK, Bonnard C, Ong RT, Thalamuthu A, Pettersson S, Liu C, Tian C, Chen WV, Carulli JP, Beckman EM, Altshuler D, Alfredsson L, Criswell LA, Amos CI, Seldin MF, Kastner DL, Klareskog L, Gregersen PK (2007) TRAF1–C5 as a risk locus for rheumatoid arthritis-a genome wide study. N Engl J Med 357:1199–1209PubMedCrossRefGoogle Scholar
  8. 8.
    Han TU, Bang SY, Kang C, Bae SC (2009) TRAF1 polymorphisms associated with rheumatoid arthritis susceptibility in Asians and in Caucasians. Arthritis Rheum 60:2577–2584PubMedCrossRefGoogle Scholar
  9. 9.
    Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F, Li W, Masters SL, Booty MG, Carulli JP, Padyukov L, Alfredsson L, Klareskog L, Chen WV, Amos CI, Criswell LA, Seldin MF, Kastner DL, Gregersen PK (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357:977–986PubMedCrossRefGoogle Scholar
  10. 10.
    Lee HS, Remmers EF, Le JM, Kastner DL, Bae SC, Gregersen PK (2007) Association of STAT4 with rheumatoid arthritis in the Korean population. Mol Med 13:455–460PubMedGoogle Scholar
  11. 11.
    Plenge RM, Cotsapas C, Davies L, Price AL, de Bakker PI, Maller J, Pe’er I, Burtt NP, Blumenstiel B, DeFelice M, Parkin M, Barry R, Winslow W, Healy C, Graham RR, Neale BM, Izmailova E, Roubenoff R, Parker AN, Glass R, Karlson EW, Maher N, Hafler DA, Lee DM, Seldin MF, Remmers EF, Lee AT, Padyukov L, Alfredsson L, Coblyn J, Weinblatt ME, Gabriel SB, Purcell S, Klareskog L, Gregersen PK, Shadick NA, Daly MJ, Altshuler D (2007) Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet 39:1477–1482PubMedCrossRefGoogle Scholar
  12. 12.
    Schreiber V, Dantzer F, Ame JC, de Murcia G (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 7:517–528PubMedCrossRefGoogle Scholar
  13. 13.
    Fougerousse F, Meloni R, Roudaut C, Beckmann JS (1999) Dinucleotide repeat polymerase in the cellular response to DNA damage, apoptosis, and disease. Am J Hum Genet 64:1282–1288CrossRefGoogle Scholar
  14. 14.
    Masutani M, Nakagama H, Sugimura T (2005) Poly(ADP-ribosyl)ation in relation to cancer and autoimmune disease. Cell Mol Life Sci 62:769–783PubMedCrossRefGoogle Scholar
  15. 15.
    Pascual M, López-Nevot MA, Cáliz R, Ferrer MA, Balsa A, Pascual-Salcedo D, Martín J (2003) A poly(ADP-ribose) polymerase haplotype spanning the promoter region confers susceptibility to rheumatoid arthritis. Arthritis Rheum 48:638–641PubMedCrossRefGoogle Scholar
  16. 16.
    Wang XG, Wang ZQ, Tong WM, Shen Y (2007) PARP1 Val762Ala polymorphism reduces enzymatic activity. Biochem Biophys Res Commun 354:122–126PubMedCrossRefGoogle Scholar
  17. 17.
    Onaran I, Tezcan G, Ozgönenel L, Cetin E, Ozdemir AT, Kanigür-Sultuybek G (2009) The Val762Ala polymorphism in the poly(ADP-ribose) polymerase-1 gene is not associated with susceptibility in Turkish rheumatoid arthritis patients. Rheumatol Int 29:797–800PubMedCrossRefGoogle Scholar
  18. 18.
    Hur JW, Sung YK, Shin HD, Park BL, Cheong HS, Bae SC (2006) Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and arthritis in systemic lupus erythematosus. Rheumatology (Oxford) 45:711–717CrossRefGoogle Scholar
  19. 19.
    Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRefGoogle Scholar
  20. 20.
    Steinbrocker O, Traeger CH, Batterman RC (1949) Therapeutic criteria in rheumatoid arthritis. J Am Med Assoc 140:659–662PubMedCrossRefGoogle Scholar
  21. 21.
    Kato N, Morita H, Sugiyama T, Kurihara H, Tsubaki S, Nabika T, Kitamura K, Yamori Y, Yazaki Y (2000) Evaluation of the poly(ADP-ribose) polymerase gene in human stroke. Atherosclerosis 148:345–352PubMedCrossRefGoogle Scholar
  22. 22.
    Cottet F, Blanché H, Verasdonck P, Le Gall I, Schächter F, Bürkle A, Muiras ML (2000) New polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity. J Mol Med 78:431–440PubMedCrossRefGoogle Scholar
  23. 23.
    Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989PubMedCrossRefGoogle Scholar
  24. 24.
    Bignon JD, Fernandez-Vina MA (1997) Protocols of the 12th international histocompatibility workshop for typing of HLA class II alleles by DNA amplification by the polymerase chain reaction (PCR) and hybridization with sequence specific oligonucleotide probes (SSOP). In: Charron D (eds) Genetic diversity of HLA: functional and medical implications. Paris, EDK, pp 584–595Google Scholar
  25. 25.
    Kotsch K, Wehling J, Blasczyk R (1999) Sequencing of HLA class II genes based on the conserved diversity of the noncoding regions: sequencing based typing of HLA-DRB genes. Tissue Antigens 53:486–497PubMedCrossRefGoogle Scholar
  26. 26.
    Lee HS, Lee KW, Song GG, Kim HA, Kim SY, Bae SC (2004) Increased susceptibility to rheumatoid arthritis in Koreans heterozygous for HLA-DRB1*0405 and *0901. Arthritis Rheum 50:3468–3475PubMedCrossRefGoogle Scholar
  27. 27.
    García S, Bodaño A, González A, Forteza J, Gómez-Reino JJ, Conde C (2006) Partial protection against collagen antibody-induced arthritis in PARP-1 deficient mice. Arthritis Res Ther 8:R14PubMedCrossRefGoogle Scholar
  28. 28.
    García S, Bodaño A, Pablos JL, Gómez-Reino JJ, Conde C (2008) Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts. Ann Rheum Dis 67:631–637PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Kyeong-A Lee
    • 1
  • So-Young Bang
    • 1
  • Byung Lae Park
    • 2
  • Jeong-Hyun Kim
    • 3
  • Hyoung Doo Shin
    • 2
    • 3
  • Sang-Cheol Bae
    • 1
    Email author
  1. 1.Department of RheumatologyHanyang University Hospital for Rheumatic DiseasesSeoulSouth Korea
  2. 2.Department of Genetic EpidemiologySNP Genetics, Inc.SeoulKorea
  3. 3.Department of Life ScienceSogang UniversitySeoulRepublic of Korea

Personalised recommendations