HLA-Cw*0602 is a predisposing allele to develop psoriatic arthritis

Czech version

Authors: M. Fojtíková ¹; J. Štolfa ¹; L. Šedová ¹; J. Gatterová ¹; J. Lippert ³; M. Černá ²
Authors‘ workplace: Revmatologický ústav, Praha, 2Institut biochemie, buněčné a molekulární biologie, 3. LF UK Praha, 3Dermatovenerologická klinika FNKV a 3. LF UK, Praha ¹
Published in: Čes. Revmatol., 17, 2009, No. 2, p. 68-73.
Category: Original Papers

Overview

Introduction:
Psoriatic arthritis (PsA) is a member of the group of spondylarthropathies. It is defined as an arthritis, generally seronegative, which accompanies psoriasis. Etiopathogenesis of this disease is not entirely clear; both environmental factors and genetic predisposition are considred. The most significant genetic predisposition for the development of PsA was identified within the short arm of the chromosome 6 in the area of major histocompatibility complex (PSORS 1).

Aim of the study:
To identify the HLA-Cw alleles of the HLA class I gene associated with a risk of development of PsA, a type of psoriasis, and development of radiographic erosions.

Methods:
A total of 102 patients with PsA were examined; they were divided according to a) occurrence of erosions in radiographic examination (erosive / nonerosive), and b) age at the onset of psoriasis manifestation (type I psoriasis with the onset of cutaneous manifestations before the 40th year of age / type II psoriasis at the age exceeding 40 years). PCR-SSP method was used for genotyping. Statistical analysis was performed using χ2 and Fischer exact test; Bonferroni test was used for multiple comparison.

Results:
1. We have found a significantly increased frequency of HLA-Cw*06 alleles in the group of patients with PsA (35.3%) in comparison with healthy Czech population (16.2%), Pc <0.05 (OR 2.43, CI 95%: 1.32-4.76). The most frequent HLA-Cw*06 allele found in both groups was HLA-Cw*0602 allele, which is associated with development of PsA in patients with psoriasis (frequency 22.5%), compared to healthy individuals (frequency 10.1%), Pc <0.05 (OR 2.74, CI 95%: 1.20-6.25). 2. HLA-Cw*0602 allele is statistically significantly associated with development of PsA in patients with type I psoriasis (allele frequency is 28.0%), compared to healthy individuals: Pc <0.05; OR 3.12; CI 95% 1.38-7.14. The frequency of this allele was comparable in the group of PsA associated with type II psoriasis and in the group of healthy individuals. We have found no significant difference in the distribution of HLA-Cw alleles depending on occurrence of erosions in radiographic examination.

Conclusion:
HLA-Cw*0602 increases the likelihood of development of PsA, mainly in patients with the onset of cutaneous manifestations before the 40th year of age. This allele is not associated with development of radiographic erosions. We have found no statistically significant differences in the distribution of other HLA-Cw alleles in patients with psoriatic arthritis.

Key words:
HLA-Cw, psoriatic arthritis, genetic predisposition

Sources

1. Moll JM, Wright V. Psoriatic arthritis. Seminars in arthritis and rheumatism 1973; 3: 55.

2. Alenius GM, Jidell E, Nordmark L, Dahlqvist SR. Disease manifestation and HLA antigens in psoriatic arthritis in Northern Sweden. Clinical Rheumatology 2002; 21: 357.

3. Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Annals of the rheumatic diseases 2005; 64 (Suppl. II), 14.

4. Shbeeb M, Gramoto KM, Gibbon LE, OęFallon WM, Gabriel SE. The epidemiology of psoriatic rthritis in Omlsted Country, Minnesota, USA, 1982-1991. J Rheumatology 2000; 27: 1247.

5. Elkayam O, Ophir J, Yaron M, Casi D. Psoriatic arthritis: interrelationships between skin and joint manifestations related to onset, course and distribution. Clinical rheumatology 2000; 19: 301.

6. Sibilia J. Psoriasis: skin and joints, same fight? Journal of the European Academy of Dermatology and Venerology 2006; 20 (Suppl. 2): 56.

7. Gladman DD, Farewell VT, Wong K, Husted J. Mortality studies in psoriatic arthritis: Results from a single center. II. Prognostic indicators for death. Arthritis Rheumatism 1998; 41: 1103.

8. Moll JM. and Wright V. Familial occurrence of psoriatic arthritis. Annals of Rheumatic Diseases 1973; 32: 181.

9. Valdimarsson H. The genetic basis of psoriasis. Clinics in Dermatology 2007; 25: 563.

10. Nair RP, Stuart P, Henseler T. Localization of psoriasis-susceptibility locus PSORS1 to a 60-kb interval telomeric to HLA-C. American Journal of Human Genetics 2000; 66, 1833.

11. Karason A, Gudjonsson JE, Upmanyu R, Antonsdottir AA, Hauksson VB, Runasdottir EH, Jonsson HH, Gudbjartsson DF, Frigge ML, KongA, Stefansson, K, Valdimarsson, H, Gulcher JR. A susceptibility gene for psoriatic arthritis maps to chromosome 16p: evidence for imprinting. American Journal of Human Genetics 2003; 72: 125.

12. Nair RP, Stuart PE, Nistor I, Hiremagalore R, Chia NV, Jenisch S, Weichenthal M, Abecasis GR, Lim HW, Christophers E, Voorhees JJ, Elder JT. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. American Journal of Human Genetics 2006; 78: 827.

13. Trembath RC, Clough RL, Rosbotham JL, Jones AB, Camp RDR, Frodsham A, Browne J, Barber R, Terwilliger J, Lathrop GM, Barker JNWN. Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Human Molecular Genetics 1997; 6: 813.

14. Martin MP, Nelson G, Lee JH, Pellett F, Gao X, Wade J, Wilson MJ, Trowsdal J, Gladman D, Carrington M. Cutting Edge: Susceptibility to Psoriatic Arthritis: Influence of Activating Killer Ig-Like Receptor Genes in the Absence of Specific HLA-C Alleles. The Journal of Imunology 2002; 169: 2818.

15. Ho YPCP, Barton A, Worthington J, Plant D, Griffiths CHEM, Young HS, Bradburn P, Thomson W, Silman AJ, Bruce IN. Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis: comparison with psoriasis and undifferentiated inflammatory arthritis. Annals of the Rheumatic Diseases 2008; 67: 677.

16. Grubic Z, Peric P, Eeéuk-Jelicic E, Zunec R, Stingl K, Curkovic B, Kerhin-Brkljacic V. () The MICA-A4 triplet repeats polymorphism in the transmembrane region confers additional risk for development of psoriatic arthritis in the Croatian population. European Journal of Immunogenetics 2004; 31: 93.

17. Gonzalez S, Martinez-Borra J, Torre-Alonso JC, Gonzales-Roces S, Sanchez del Rio J, Perez R, Brautbar Ch, Lopez-Larrea C. The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to develop psoriatic arthritis, and is independent of the association of Cw*0602 in psoriasis. Arthritis and Rheumatism 1999; 42: 1010.

18. Sczcerkowska Dobosz A, Rebala K, Szczerkowska Z, Nedoszytko B. HLA-C locus alleles distribution in patients from nothern Poland with psoriatic arthritis: preliminary report. International Journal of Immunogenetics 2005; 32: 389.

19. Gudjonsson JE, Karason A, Runarsdottir EH, Antonsdottir AA, Hauksson VB, Jónsson HH, Gulcher J, Stefansson K, Valdimarsson H. Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients--an analysis of 1019 HLA-C- and HLA-B-typed patients. Journal of Investigative Dermatology 2006; 126: 740.

20. Mallon E, Bunce M, Wojnarowska F, Welsh K. HLA-Cw*0602 is a susceptibility factor in type I psoriasis, and evidence Ala-73 is increased in male type I psoriasis. Journal of Investigative Dermatology 1997; 109: 183.

21. Gladman DD, Cheung C, Ng CM, Wade JA. HLA-C locus alleles in patients with psoriatic arthritis (PsA). Human Imunology 1999; 60: 259.

22. Queiro R, Torre JC, Gonzales S, Lopez-Larrea C, Tinture T, Lopez-Lagunas I. HLA antigens may influence the age of onset of psoriasis and psoriatic arthritis. The Journal of Rheumatology 2003; 30: 505.

23. Queiro R, Gonzales S, Lopez-Larrea C, Alperi M, Sarasqueta C, Riestra JL, Ballina J. HLA-C locus alleles may modulate the clinical expression of psoriatic arthritis. Arthritis Research and Therapy 2006; 8: R185.

24. Gambelunghe G, Ghaderi M, Cosentino A, Falorni A na Ad, Brunetti P, Falorni Ad, Sanjeevi CB. Association of MHC class I chain-related A (MIC-A) gene polymorphism with type I diabetes. Diabetologia 2000; 4: 507.

25. Gambelunghe G, Ghaderi M, Tortoioli C, Falorni A, Santeusanio F, Brunetti P, Sanjeevi CB, Falorni A. Two distinct MICA gene markers discriminate major autoimmune diabetes types. The Journal of Clinical Endocrinology & Metabolism 2001; 8: 3754.

26. Novota P, Kolostova K, Pinterova D, Novak J, Weber P, Treslova L, Kovar J, Andel M, Cerna M. Association of MHC class I chain related gene-A microsatellite polymorphism with the susceptibility to T1DM and LADA in Czech adult patients. International Journal of Immunogenetics 2005; 32, 273.

27. Cerna M, Kolostova K, Novota P, Romzova M, Cejkova P. Pinterova D. Pruhova S, Treslova L, Andel M. Autoimmune diabetes mellitus with adult onset and type 1 diabetes mellitus in children have different genetic predispositions. Annals of the NewYork Academy of Science 2007; 1110, 140.

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Article was published in

Czech Rheumatology

2009 Issue 2