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01-08-2016 | Genes and Disease

Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis

Authors: Hala M. Raslan, Hanaa R. Attia, Iman Salama, Mona Hamed Ibrahim, Eman Mahmoud Hassan, Mohamed S. El Hussieny, Manal M. El Menyawi, Khalda S. Amr

Published in: Rheumatology International | Issue 8/2016

Abstract

To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5–3.5) and bone erosion (OR = 2.9, 95 % CI 1.1–7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9–204.4 for RA and OR = 69.4, 95 % CI 15.8–305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.

Shukla S, Tripathi AK, Tripathi JK, Indurkar M, Chauhan UK (2014) Role of PTPN22 and VDR gene polymorphisms in susceptibility to rheumatoid arthritis: a study from central India. Adv Genom Genet 4:79–85CrossRef

Plant D, Thomson W, Lunt M, Flynn E, Martin P, Eyre S, Farragher T, Bunn D, Worthington J, Symmons D, Barton A (2011) The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register. Rheumatology 50:78–84CrossRefPubMed

Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith A, Spoerke JM et al (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75:330–337CrossRefPubMedPubMedCentral

Harrison P, Pointon J, Farrar C, Brown MA, Wordsworth BP (2006) Effects of PTPN22 C1858T polymorphism on susceptibility and clinical characteristics of British Caucasian rheumatoid arthritis patients. Rheumatology 45:1009–1011CrossRefPubMed

Lee AT, Li W, Liew A, Bombardier C, Weisman M, Massarotti EM, Kent J, Wolfe F, Begovich AB, Gregersen PK (2005) The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status. Genes Immun 6:129–133CrossRefPubMed

Steer S, Lad B, Grumley JA, Kingsley GH, Fisher SA (2005) Association of R602W in a protein tyrosine phosphatase gene with a high risk of rheumatoid arthritis in a British population: evidence for an early onset/disease severity effect. Arthritis Rheum 52:358–360CrossRefPubMed

Hinks A, Barton A, John S, Bruce I, Hawkins C, Griffiths CE, Donn R, Thomson W, Silman A, Worthington J (2005) Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis Rheum 52:1694–1699CrossRefPubMed

Orozco G, Sanchez E, Gonzalez-Gay MA, Lopez-Nevot MA, Torres B, Caliz R, Ortego-Centeno N, Jiménez-Alonso J, Pascual-Salcedo D, Balsa A (2005) Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Rheum 52:219–224CrossRefPubMed

Zhernakova A, Eerligh P, Wijmenga C, Barrera P, Roep BO, Koeleman BP (2005) Differential association of the PTPN22 coding variant with autoimmune diseases in a Dutch population. Genes Immun 6:459–461CrossRefPubMed

10.

Naseem H, Thomson W, Silman A, Worthington J, Symmons D, Barton A (2008) The PTPN22*C1858T functional polymorphism is associated with susceptibility to inflammatory polyarthritis but neither this nor other variants spanning the gene is associated with disease outcome. Ann Rheum Dis 67:251–255CrossRefPubMedPubMedCentral

11.

Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMed

12.

Prevoo ML, Van’t Hof MA, Kuper RH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38(1):44–48CrossRefPubMed

13.

Kaarela K, Kautiainen H (1997) Continuous progression of radiological destruction in seropositive rheumatoid arthritis. J Rheumatol 24:1285–1287PubMed

14.

Kindmark CO (1972) The concentration of C-reactive protein in Sera from healthy individuals. Scand J Clin Lab Invest 29:407–411CrossRefPubMed

15.

Ernst E, Espersen G, Andersen M, Grunnet N (1988) RF-classes (IgM, IgG, IgA) in a group of highly active RA-patients in relation to disease activity and treatment. Scand J Rheumatol Suppl 75:250–255CrossRefPubMed

16.

Bizzaro N, Mazzanti G, Tonutti E, Villalta D, Tozzoli R (2001) Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid. Arthritis Clin Chem 47:1089–1093PubMed

17.

Jawaheer D, Gregersen PK (2002) Rheumatoid arthritis: the genetic components. Rheum Dis Clin North Am 28:1–15CrossRefPubMed

18.

De Rycke L, Peene I, Hoffman IE, Kruithof E, Union A, Meheus L, Lebeer K, Wyns B, Vincent C, Mielants H, Boulart L, Serre GM, Veys EM, de Keyser F (2004) Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rhem Dis 63:1587–1593CrossRef

19.

Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP (2011) Why is PTPN22 a good candidate susceptibility gene for autoimmune with RA disease? FEBS Lett 585:3689–3698CrossRefPubMed

20.

Hashemi M, Atabaki M, Daneshvar H, Zakeri Z, Eskandari-Nasab E (2013) Association of PTPN22 rs2476601 and EGFR rs17337023 Gene polymorphisms and rheumatoid arthritis in Zahedan, Southeast Iran. Int J Immunogenet 40(4):299–305CrossRefPubMed

21.

Totaro MC, Tolusso B, Napolioni V, Faustini F, Canestri S, Mannocci A, Gremese E, Bosello EL, Alivernini S (2011) Ferraccioli G PTPN22 1858C > T polymorphism distribution in Europe and association with rheumatoid arthritis: case–control study and meta-analysis. PLoS One 6(9):e24292CrossRefPubMedPubMedCentral

22.

Torres-Carrillo NM, Ruiz-Noa Y, Martinez-Bonilla GE, Leyva-Torres SD, Torres-Carrillo N, Palafox-Sanchez CA, Navarro-Hernandez RE, Rangel-Villalobos H, Oregon-Romero E, Munoz-Valle JF (2012) The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico. Immunol Lett 147:41–46CrossRefPubMed

23.

Song GG, Bae SG, Kim JH, Lee YH (2013) The PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis. Rheumatol Int 33(8):1991–1999CrossRefPubMed

24.

Orozco G, Pascual-Salcedo D, LÓpez-Nevot MA, Cobo T, CabezÓn T, MartÍn-Mola E, Balsa A, MartÍn J (2008) Auto-antibodies, HLA and PTPN22: susceptibility markers for rheumatoid arthritis. Rheumatology 47:138–141CrossRefPubMed

25.

Sahin N, Gunduz F, Inanc N, Direskeneli H, Saruhan-Direskeneli D (2009) No association of PTPN22 gene polymorphism with rheumatoid arthritis inTurkey. Rheumatol Int 30(1):81–83CrossRefPubMed

26.

Zhebrun D, Kudryashova Y, Babenko A, Maslyansky A, Kunitskaya N, Popcova D, Klushina A, Grineva E, Kostareva A, Shlyakhto E (2011) Association of PTPN22 1858T/T genotype with type 1 diabetes, Graves’ disease but not with rheumatoid arthritis in Russian population. Aging (Albany NY) 3(4):368–373CrossRef

27.

Ikari K, Momohara S, Inoue E, Tomatsu T, Hara M, Yamanaka H, Kamatani N (2006) Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population. Rheumatology (Oxford) 45(11):1345–1348CrossRef

28.

Li Q, Lin KQ, Li Q, Wang J, Yu J, Yu L, Yi W, Huang XQ, Chu JY, Yang ZQ (2013) Association of polymorphisms of PTPN22 and PADI4 genes with rheumatoid arthritis in Yunnan. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 30(1):111–115PubMed

29.

Lie BA, Viken MK, Odegard S, van der Heijde D, Landewé R, Uhlig T, Kvien TK (2007) Associations between the PTPN22 1858C-T polymorphism and radiographic joint destruction in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 66(12):1604–1609CrossRefPubMedPubMedCentral

30.

Morgan AW, Robinson JI, Conaghan PG, Martin SG, Hensor EMA, Morgan MD, Steiner L, Erlich HA, Gooi H, Barton A, Worthington J, Emery P (2010) Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort. Arthritis Res Ther 12:R57CrossRefPubMedPubMedCentral

31.

Garcia-Melendez ME, Salinas-Santander M, Sanchez-DOminguez C, Gonzalez-Cardenas H, Cerda-Flores RM, Ocampo-Candiani J, Ortiz-López R (2014) Protein tyrosine phosphatase PTPN22 +1858C/T polymorphism is associated with active vitiligo. Exp Ther Med 8:1433–1437PubMedPubMedCentral

32.

Klimiuk PA, Yang H, Goronzy JJ, Weyand CM (1999) Production of cytokines and metalloproteinases in rheumatoid synovitis is T cell dependent. Clin Immunol 90:65–78CrossRefPubMed

33.

O’Dell JR, Nepom BS, Haire C, Gersuk VH, Gaur L, Moore GF, Drymalski W, Palmer W, Eckhoff PJ, Klassen LW, Wees S, Thiele G (1998) Nepom GT HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments. Ann Rheum Dis 57:209–213CrossRefPubMedPubMedCentral

34.

Fries JF, Wolfe F, Apple R, Erlich H, Bugawan T, Holmes T, Bruce B (2002) HLA–DRB1 Genotype Associations in 793 white patients from a rheumatoid arthritis inception cohort frequency, severity, and treatment bias. Arthritis Rheum 46(9):2320–2329CrossRefPubMed

35.

Kokkonen H, Brink M, Hansson M, Lassen E, Mathsson-Alm L, Holmdahl R, Rönnelid J, Klareskog L, Rantapää-Dahlqvist S (2015) Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis. Arthritis Res Ther 17:125–139CrossRefPubMedPubMedCentral

36.

Bang S, Han T, Choi C, Sung Y, Bae S, Kang C (2010) Peptidyle arginine deiminase type IV (PADI4) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study. Arthritis Res Ther 12:R115–R123CrossRefPubMedPubMedCentral

37.

Kuru O, Bilgici A, Birinci A, Ulusoy H, Durupinar B (2009) Prognostic value of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis. Brastil Lek Listy 110(10):650–654

38.

Ateş A, Kinikli G, Turgay M, Akay G, Tokgöz G (2007) Effects of rheumatoid factor isotypes on disease activity and severity in patients with rheumatoid arthritis: a comparative study. Clin Rheumatol 26(4):538–545CrossRefPubMed

Title: Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis
Authors: Hala M. Raslan
Hanaa R. Attia
Iman Salama
Mona Hamed Ibrahim
Eman Mahmoud Hassan
Mohamed S. El Hussieny
Manal M. El Menyawi
Khalda S. Amr
Publication date: 01-08-2016
Publisher: Springer Berlin Heidelberg
Published in: Rheumatology International / Issue 8/2016
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-016-3511-6

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