Abstract
The aim of this study was to perform an association study between two single nucleotide polymorphisms (SNPs) rs2910164 G>C and rs3746444 T>C in pre-miRNA (hsa-mir-146a and hsa-mir-499) and rheumatoid arthritis (RA) in the Han Chinese population. 208 Han Chinese patients with RA and 240 healthy controls were recruited in this study. The SNPs was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Anti-cyclic citrullinated peptide (anti-CCP) antibody was measured by enzyme linked immunosorbent assay and rheumatoid factor (RF) was measured by rate nephelometry. The genotype frequencies between cases and controls were compared by χ2 analysis. No significant association between the SNPs (rs2910164 and rs3746444) and RA was observed (P = 0.631 and 0.775, respectively), and the SNPs did not show any association with the RF-positive (P = 0.631 and 0.775, respectively). However, there was a significant difference on the level of anti-CCP antibody between different genotypes in rs3746444 (P = 0.007). The heterozygote CT had significantly higher level of anti-CCP antibody compared with homozygote CC and TT (P = 0.054 and 0.003, respectively). We first investigated the association between the SNPs (rs2910164 G>C and rs3746444 T>C) in the pre-miRNA (hsa-mir-146a and hsa-mir-499) and RA in a Han Chinese population. We did not find a significant association between the SNPs and the susceptibility to RA, while the SNP rs3746444 may affect anti-CCP antibody production.
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References
Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P (2007) New therapies for treatment of rheumatoid arthritis. Lancet 370:1861–1874
Lipsky PE, Van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden J et al (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 343:1594–1602
Lee UJ, Choung SR, Prakash KV, Lee EJ, Lee MY, Kim YJ, Han CW, Choi YC (2008) Dual knockdown of p65 and p50 subunits of NF-kappaB by siRNA inhibits the induction of inflammatory cytokines and significantly enhance apoptosis in human primary synoviocytes treated with tumor necrosis factor-alpha. Mol Biol Rep 35(3):291–298
Thabet MM, Wesoly J, Slagboom PE, Toes RE, Huizinga TW (2007) FCRL3 promoter 169 CC homozygosity is associated with susceptibility to rheumatoid arthritis in Dutch Caucasians. Ann Rheum Dis 66:803–806
Raychaudhuri S, Thomson BP, Remmers EF, Eyre S, Hinks A, Guiducci C (2009) Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet 41:1313–1318
Orozco G, Hinks A, Eyre S, Ke X, Gibbons LJ, Bowes J et al (2009) Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23. Hum Mol Genet 18(14):2693–2699
Gandjbakhch F, Fajardy I, Ferré B, Dubucquoi S, Flipo RM, Roger N et al (2009) A functional haplotype of PADI4 gene in rheumatoid arthritis: positive correlation in a French population. J Rheumatol 36(5):881–886
Fabbri M, Croce CM, Calin GA (2008) MicroRNAs. Cancer J 14:1–6
Lodish HF, Zhou B, Liu G, Chen CZ (2008) Micromanagement of the immune system by microRNAs. Nat Rev Immunol 8:120–130
Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114
Krek A, Gru¨n D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500
Saunders MA, Liang H, Li WH (2007) Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA 104:3300–3305
Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309:1519–1524
Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G et al (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–161
Cobb BS, Hertweck A, Smith J, O’Connor E, Graf D, Cook T et al (2006) A role for Dicer in immune regulation. J Exp Med 203:2519–2527
Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK (2008) Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 10(4):1–10
Hillyer P, Larché MJ, Bowman EP, McClanahan TK, de Waal Malefyt R, Schewitz LP et al (2009) Investigating the role of the interleukin-23/-17A axis in rheumatoid arthritis. Rheumatology 48(12):1581–1589
Ying B, Shi Y, Pan X, Song X, Huang Z, Niu Q, Cai B, Wang L (2011) Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. Mol Biol Rep 38(1):379–385
Yuan FL, Hu W, Lu WG, Li X, Li JP, Xu RS, Li CW, Chen FH, Jin C (2010) Targeting interleukin-21 in rheumatoid arthritis. Mol Biol Rep Biol Rep. doi:10.1007/s11033-010-0285-x
Huang CH, Cong L, Xie J, Qiao B, Lo SH, Zheng T (2009) Rheumatoid arthritis-associated gene-gene interaction network for rheumatoid arthritis candidate genes. BMC Proc 15(3 Suppl 7):S75
Lin SC, Kuo CC, Chan CH (2006) Association of a BTLA gene polymorphism with the risk of rheumatoid arthritis. J Biomed Sci 13(6):853–860
van Gaalen FA, van Aken J, Huizinga TWJ, GMTh Schreuder, Breedveld FC, Zanelli E et al (2004) Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis. Arthritis Rheum 50:2113–2121
Senkpiehl I, Marget M, Wedler M, Jenisch S, Georgi J, Kabelitz D et al (2005) HLA-DRB1 and anti-cyclic citrullinated peptide antibody production in rheumatoid arthritis. Int Arch Allergy Immunol 137:315–318
Loktionov A (2004) Common gene polymorphisms, cancer progression and prognosis. Cancer Lett 208(1):1–33
Calin GA, Ferracin M, Cimmino A, Leva GD, Shimizu M, Wojcik SE et al (2005) A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353:1793–1801
Duan R, Pak C, Jin P (2007) Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet 16:1124–1131
Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN (2006) Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 125:887–901
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L et al (2008) Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest 118:2600–2608
Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M et al (2008) Expression of MicroRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 58(5):1284–1292
Li-Fan Lu, Liston Adrian (2009) MicroRNA in the immune system, microRNA as an immune system. Immunology 127:291–298
Van der Helm-van Mil AHM, Huizinga TWJ (2008) Advances in the genetics of rheumatoid arthritis point to subclassification into distinct disease subsets. Arthritis Res Ther 10:205
Ji JD, Lee WJ, Kong KA, Woo JH, Choi SJ, Lee YH, Song GG (2010) Association of STAT4 polymorphism with rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 37(1):141–147
Kobayashi S, Ikari K, Kaneko H, Kochi Y, Yamamoto K, Shimane K et al (2008) Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population. Arthritis Rheum 58:1940–1946
Suzuki A, Yamada R, Chang X et al (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34:395–402
Harney SM, Meisel C, Sims AM, Woon PY, Wordsworth BP, Brown MA (2005) Genetic and genomic studies of PADI4 in rheumatoid arthritis. Rheumatology 44:869–872
Schellekens GA, Visser H, de Jong BA, Van den Hoogen FH, Hazes JM, Breedveld FC et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163
Chavanas S, Mechin MC, Takahara H, Kawada A, Nachat R, Serre G et al (2004) Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6. Gene 330:19–27
Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ (2003) PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25:1106–1118
Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B et al (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106(5):1502–1505
Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD et al (2009) A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 9:1–6
Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY et al (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29(11):2126–2131
Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B et al (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106:1502–1505
Egerer K, Feist E, Burmester GR (2009) The serological diagnosis of rheumatoid arthritis: antibodies to citrullinated antigens. Dtsch Arztebl Int 106(10):159–163
Raptopoulou A, Sidiropoulos P, Katsouraki M, Boumpas DT (2007) Anti-citrulline antibodies in the diagnosis and prognosis of rheumatoid arthritis: evolving concepts. Crit Rev Clin Lab Sci 44(4):339–363
Avouac J, Gossec L, Dougados M (2006) Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65(7):845–851
Nieword TB, Harrison MJ, Paget SA (2007) Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. Q J Med 100:193–201
Acknowledgments
The authors thank the participating RA patients and their families. The authors acknowledge the grant support from the National Natural Science Foundation of China (Grant No. 30670819, 30900658, 30772051 and 30950010).
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LanLan Wang and BinWu Ying contributed equally to this work.
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11033_2010_633_MOESM1_ESM.doc
Supplementary Figure 1f: The relation between anti-CCP antibody and Frequency distribution of SNP rs2910164 G > C genotypes in RA patients (A) and female RA patients (B) (A) The median of anti-CCP antibody in genotype CC was 119.16 RU/ml (9.51–196.65); The median of anti-CCP antibody in genotype CG was 135.53 RU/ml (17.55–235.75); The median of anti-CCP antibody in genotype GG was 156.06 RU/ml (18.35–273.51); There was no significant difference between different genotypes (P = 0.554). (B) The median of anti-CCP antibody in genotype CC was 106.49 RU/ml (9.69–222.87). The median of anti-CCP antibody in genotype CG was 120.47 RU/ml (16.33–235.66). The median of anti-CCP antibody in genotype GG was 151.35 RU/ml (11.09–287.61). There was no significant difference between different genotypes (P = 0.736). (DOC 115 kb)
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Yang, B., Zhang, J.L., Shi, Y.Y. et al. Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid arthritis in a Han Chinese population. Mol Biol Rep 38, 4913–4919 (2011). https://doi.org/10.1007/s11033-010-0633-x
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DOI: https://doi.org/10.1007/s11033-010-0633-x