CLINICAL IMMUNOLOGY
Association of the TNF-α, IL-2, and IL-2RB gene variants with susceptibility to psoriasis in a Turkish cohort
Submission date: 2016-12-06
Final revision date: 2017-03-23
Acceptance date: 2017-03-27
Publication date: 2018-03-30
Cent Eur J Immunol 2018;43(1):50-57
KEYWORDS
ABSTRACT
Aim of the study:
The aim of this study was to investigate the role TNF-α, IL-2, and IL-2RB variants in psoriasis (Ps) and to evaluate the association between these variants and clinical features.
Material and methods:
A total of 74 psoriatic patients and 74 healthy individuals were genotyped for these variants by PCR and/or RFLP.
Results:
The AA genotype of TNF-α (–308) was significantly more common in the patients (p = 0.013). TNF-α (–238) AA genotype was significantly increased in the patients (p = 0.028), while the GG genotype was decreased in the patient group, compared to the controls (p = 0.016). IL-2 (–330) variant GG and TT genotype was more common in the patients (p = 0.037, p = 0.009, respectively), while IL-2 (–330) GT genotype was increased in the control subjects (p = 0.001). IL-2 (–330) GG genotype frequency was significantly decreased (p = 0.021) and the TT genotype frequency was significantly increased among patients with psoriatic arthritis in comparison with Ps patients (p = 0.014). IL-2RB TC genotype frequency was significantly decreased and TT genotype frequency was significantly increased in the patients with positive family history of Ps compared to those who had a negative family history (p = 0.017, p = 0.014, respectively). Also, IL-2RB CC genotype was significantly increased among the patients with late-onset Ps in comparison with the early onset Ps group (p = 0.009). The frequency of IL-2 (–330) TT genotype was significantly higher in mild Ps patients than moderate-severe patients (p = 0.043).
Conclusions:
Our data suggest a potential role of these genes as candidate genes for susceptibility to Ps in a Turkish cohort.
The aim of this study was to investigate the role TNF-α, IL-2, and IL-2RB variants in psoriasis (Ps) and to evaluate the association between these variants and clinical features.
Material and methods:
A total of 74 psoriatic patients and 74 healthy individuals were genotyped for these variants by PCR and/or RFLP.
Results:
The AA genotype of TNF-α (–308) was significantly more common in the patients (p = 0.013). TNF-α (–238) AA genotype was significantly increased in the patients (p = 0.028), while the GG genotype was decreased in the patient group, compared to the controls (p = 0.016). IL-2 (–330) variant GG and TT genotype was more common in the patients (p = 0.037, p = 0.009, respectively), while IL-2 (–330) GT genotype was increased in the control subjects (p = 0.001). IL-2 (–330) GG genotype frequency was significantly decreased (p = 0.021) and the TT genotype frequency was significantly increased among patients with psoriatic arthritis in comparison with Ps patients (p = 0.014). IL-2RB TC genotype frequency was significantly decreased and TT genotype frequency was significantly increased in the patients with positive family history of Ps compared to those who had a negative family history (p = 0.017, p = 0.014, respectively). Also, IL-2RB CC genotype was significantly increased among the patients with late-onset Ps in comparison with the early onset Ps group (p = 0.009). The frequency of IL-2 (–330) TT genotype was significantly higher in mild Ps patients than moderate-severe patients (p = 0.043).
Conclusions:
Our data suggest a potential role of these genes as candidate genes for susceptibility to Ps in a Turkish cohort.
REFERENCES (42)
1.
Chomiczewska-Skóra D, Trznadel-Grodzka E, Rotsztejn H (2013): Psoriasis as a disease associated with the immune system disorders. Centr Eur J Immunol 38: 129-133.
2.
Chandra A, Ray A, Senapati S, et al. (2015): Genetic and epigenetic basis of psoriasis pathogenesis. Mol Immunol 64: 313-323.
3.
Baliwag J, Barnes DH, Johnston A (2015): Cytokines in psoriasis. Cytokine 73: 342-350.
4.
Karam RA, Zidan HE, Khater MH (2014): Polymorphisms in the TNF- and IL-10 gene promoters and risk of psoriasis and correlation with disease severity. Cytokine 66: 101-105.
5.
Malek TR, Bayer AL (2004): Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 4: 665-674.
6.
Togawa S, Joh T, Itoh M, et al. (2005): Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection. Helicobacter 10: 172-178.
7.
Hoffmann SC, Stanley EM, Darrin Cox E, et al. (2001): Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 72: 1444-1450.
8.
Pál Z, Antal P, Millinghoffer A, et al. (2010): A novel galectin-1 and interleukin 2 receptor haplotype is associated with autoimmune myasthenia gravis. J Neuroimmunol 229:.
10.
Wu HC, Chang CH, Wan L, et al. (2006): IL-2 gene C/T polymorphism is associated with prostate cancer. J Clin Lab Anal 20: 245-249.
11.
de Rie MA, Goedkoop AY, Bos JD (2004): Overview of psoriasis. Dermatol Ther 17: 341-349.
12.
Miller SA, Dykes DD, Polesky HF (1998): A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215.
13.
Akcali A, Pehlivan S, Pehlivan M, et al. (2010): TNF-αlpha promoter polymorphisms in multiple sclerosis: no association with -308 and -238 alleles, but the -857 alleles in associated with the disease in Turkish patients. Int J Immunogenet 37: 91-95.
15.
Schlaak JF, Buslau M, Jochum W, et al. (1994): T cells involved in psoriasis vulgaris belong to the Th1 subset. J Invest Dermatol 102: 145-149.
16.
Kastelan D, Kastelan M, Massari LP, et al. (2006): Possible association of psoriasis and reduced bone mineral density due to increased TNF-αlpha and IL-6 concentrations. Med Hypotheses 67: 1403-1405.
17.
Abanmi A, Al Harthi F, Al Agla R, et al. (2005): Serum levels of pro-inflammatory cytokines in psoriasis patients from Saudi Arabia. Int J Dermatol 44: 82-83.
18.
Wilson AG, de Vries N, Pociot F, et al. (1993): An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med 177: 557-560.
19.
D’Alfonso S, Richiardi PM (1994): A polymorphic variation in a putative regulation box of the TNF-A promoter region. Immunogenetics 39: 150-155.
20.
Wilson AG, Symons JA, McDowell TL, et al. (1997): Effects of a polymorphism in the human tumor necrosis factor promoter on transcriptional activation. Proc Natl Acad Sci 94: 3195-3199.
21.
Danis VA, Millington M, Hyland V, et al. (1995): Increased frequency of the uncommon allele of a tumour necrosis factor alpha gene polymorphism in rheumatoid arthritis and systemic lupus erythematosus. Dis Markers 12: 127-133.
22.
Kaluza W, Reuss E, Grossmann S, et al. (2000): Different transcriptional activity and in vitro TNF-αlpha production in psoriasis patients carrying the TNF-αlpha 238A promoter polymorphism. J Invest Dermatol 114: 1180-1183.
23.
Cabaleiro T, Román M, Gallo E, et al. (2013): Association between psoriasis and polymorphisms in the TNF, IL12B, and IL23R genes in Spanish patients. Eur J Dermatol 23: 640-645.
24.
Gallo E, Cabaleiro T, Román M, et al. (2012): Study of genetic polymorphisms in the tumor necrosis factor promoter region in Spanish patients with psoriasis. Actas Dermosifiliogr 103: 301-307.
25.
Arias AI, Giles B, Eiermann TH, et al. (1997): Tumor necrosis factor-alpha gene polymorphism in psoriasis. Exp Clin Immunogenet 14: 118-122.
26.
Nedoszytko B, Szczerkowska-Dobosz A, Zabłotna M, et al. (2007): Associations of promoter region polymorphisms in the tumour necrosis factor-alpha gene and early-onset psoriasis vulgaris in a northern Polish population. Br J Dermatol 157: 165-167.
27.
Höhler T, Grossmann S, Stradmann-Bellinghausen B, et al. (2002): Differential association of polymorphisms in the TNF region with psoriatic arthritis but not psoriasis. Ann Rheum Dis 61: 213-218.
28.
Long F, Sun C, Deng D, et al. (2004): TNF-238A is associated with juvenile onset psoriasis in patients of Han population in Southwest China. J Dermatol Sci 36: 109-111.
29.
Zhuang L, Ma W, Cai D, et al. (2013): Associations between tumor necrosis factor- polymorphisms and risk of psoriasis: a meta-analysis. PLoS One 8: e68827.
30.
Baran W, Szepietowski JC, Mazur G, et al. (2006): A –308 promoter polymorphism of tumor necrosis factor alpha gene does not associate with the susceptibility to psoriasis vulgaris. No difference either between psoriasis type I and.
32.
Kim TG, Pyo CW, Hur SS, et al. (2003): Polymorphisms of tumor necrosis factor (TNF) alpha and beta genes in Korean patients with psoriasis. Arch Dermatol Res 295: 8-13.
33.
Chang YT, Chou CT, Yu CW, et al. (2007): Cytokine gene polymorphisms in Chinese patients with psoriasis. Br J Dermatol 156: 899-905.
34.
Höhler T, Kruger A, Schneider PM, et al. (1997): A TNF- promoter polymorphism is associated with psoriasis and psoriatic arthritis. J Invest Dermatol 109: 562-565.
35.
Hamamoto Y, Tateno H, Ishida T, et al. (2000): Lack of association between promoter polymorphism of the tumor necrosis factor-alpha gene and psoriatic arthritis in Japanese patients. J Invest Dermatol 115: 1162-1164.
36.
Nishibu A, Oyama N, Nakamura K, et al. (2002): Lack of association of TNF-238A and -308A in Japanese patients with psoriasis vulgaris, psoriatic arthritis and generalized pustular psoriasis. J Dermatol Sci 29: 181-184.
37.
Sadlack B, Löhler J, Schorle H, et al. (1995): Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur J Immunol 25: 3053-3059.
38.
Roussaki-Schulze AV, Kouskoukis C, Petinaki E, et al. (2005): Evaluation of cytokine serum levels in patients with plaque-type psoriasis. Int J Clin Pharmacol Res 25: 169-173.
39.
Roh NK, Han SH, Youn HJ, et al. (2015): Tissue and Serum Inflammatory Cytokine Levels in Korean Psoriasis Patients: a Comparison between Plaque and Guttate Psoriasis. Ann Dermatol 27: 738-743.
40.
Warren RB, Smith RL, Flynn E, et al. (2011): A systematic investigation of confirmed autoimmune loci in early-onset psoriasis reveals an association with IL2/IL21. Br J Dermatol 164: 660-664.
41.
Kim YK, Pyo CW, Choi HB, et al. (2007): Associations of IL-2 and IL-4 gene polymorphisms with psoriasis in the Korean population. J Dermatol Sci 48: 133-139.
42.
Zhou J, Wang L, Wang F, et al. (2015): 4q27 as a psoriasis susceptibility locus in the Northeastern Chinese Han population. Tissue Antigens 85: 15-19.
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
