The association of TNFα -238 G/A gene polymorphism with alopecia areata

Abstract

Background/Aim: Alopecia areata (AA), which is characterized by hair loss, is an inflammatory autoimmune disease. Tumor necrosis factor-alpha (TNFα) is a potent proinflammatory cytokine that has a highly significant role in inflammatory and immune responses. The aim of this study is to evaluate whether there is a relationship between TNFα -238 G/A gene polymorphism and AA in the Turkish population. Methods: In this case-control study, the frequency of TNFα-238 G/A gene polymorphism and its relationship with some clinical parameters of AA patients were investigated. Seventy-eight AA patients and 78 healthy individuals were included in our study. TNFα -238 G/A polymorphism was evaluated by the PCR-RFLP method. Results: The distribution of TNFα -238 G/A genotypes was significantly different between patients and control subjects (P<0.001). Frequency of genotypes GG and AA in AA patients (53.8 and 6.4%, respectively) were evidently lower compared to the controls (59 and 25.6%, respectively). Individuals with AA genotype had a lower risk of AA disease [odds ratio (OR)=0.27; 95% CI=0.09-0.79; relative risk (RR)=0.65 (0.49-0.86); P=0.013]. GA genotype was significantly higher in patients with AA (39.7%) compared to the control group (15.4%) and an increased risk of patchy AA was observed [OR=2.82, 95% CI=1.28-6.21; RR=1.87 (1.11-3.15); P=0.008]. Conclusion: These results suggest that the TNFα -238 G/A gene polymorphism is associated with AA and individuals with GA genotype may have an increased risk of AA.

Keywords

• TNFα
• Gene polymorphism
• Alopecia areata

References

1. 1. Safavi KH, Muller SA, Suman VJ et al. Incidence of alopecia areata in Olmsted County. Minnesota, 1975 through 1989. Mayo Clin Proc. 1995;70:628-33.
2. 2. Dizen-Namdar N, Kocak FE, Kidir M et al. Evaluation of serum paraoxonase, arylesterase, prolidase activities and oxidative stress in patients with alopecia areata. Skin Pharmacol Physiol. 2019;32:59-64.
3. 3. Cristina CS, Mauricio SS, Armando LR et al. Tumor necrosis factor alpha promoter- 308 G/A polymorphism in Mexican patients with patchy alopecia areata. Int J Dermatol. 2012;51:571-5.
4. 4. Gillian M. Galbraith R, Pandey JR. Tumor necrosis factor alpha gene polymorphism in alopecia areata. Hum Genet. 1995;96:433-6.
5. 5. Chen L, Huang Z, Liao Y, et al. Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis. Braz J Med Biol Res. 2019;52(3):e7927.
6. 6. Aisha NM, Haroon J, Hussain S et al. Association between tumour necrosis-a gene polymorphisms and acne vulgaris in a Pakistani population. Clin Exp Dermatol. 2016;41:297-301.
7. 7. Rajesh D, Gurumurthy R, Kutty AV, Balakrishna S. Tumor necrosis factor alpha gene promoter -238G/A polymorphism increases the risk of psoriasis vulgaris in Indian patients. Int J Dermatol. 2017;56(3):307-11.
8. 8. Gilhar A, Paus R, Kalish RS. Lymphocytes, neuropeptides, and genes involved in alopecia areata. J Clin Invest. 2007;117:2019-27.

9. 9. Olsen E, Hordinsky M, Price V et al. Alopecia areata investigational assessment guidelines – part II. J Am Acad Dermatol. 2004;51:440-7.
10. 10. Tan FM, Yao HF, Lu HQ, Chen SQ. Study on the polymorphism of TNFα -238G/A and -308G/A gene in patients with alopecia areata. Journal of Clinical Dermatology. 2012;41(6):342-5.
11. 11. Gulel A, Inaloz HS, Nursal AF et al. Association of the TNF-α, IL-2, and IL-2RB gene variants with susceptibility to psoriasis in a Turkish cohort. Cent Eur J Immunol. 2018;43(1):50-7.
12. 12. Xu Y, Cao X, Jiang J et al. TNF-α-308/- 238 polymorphisms are associated with gastric cancer: A casecontrol family study in China. Clin Res Hepatol Gastroenterol. 2016;41:103-9.
13. 13. Yu JY, Li L, Ma H et al. Tumor necrosis factor-a 238 G/A polymorphism and gastric cancer risk: A meta-analysis. Tumor Biol. 2013;34:3859-63.
14. 14. Shafia S, Sofi FA, Dilafroze et al. The association between TNFα gene polymorphisms and susceptibility to rheumatoid arthritis in an ethnic Kashmiri population: relationship with disease activity and severity markers. Int J Rheum Dis. 2016;19(4):362-9.
15. 15. Brinkman BMN, Huizinga TWJ, Kurban SS et al. Tumour Necrosis Factor a Gene polymorphisms in Rheumatoid arthritis: associated with susceptibility to/or severity of disease. Br J Rheumatol. 1997;36:516-21.
16. 16. Fabris M, Di Poi E, Sacco S et al. TNF- alpha gene polymorphisms in rheumatoid arthritis patients treated with anti-TNF-alpha agents: preliminary results. Reumatismo. 2002;54(1):19-26.
17. 17. Szabó K, Tax G, Teodorescu-Brinzeu D et al. TNFα gene polymorphisms in the pathogenesis of acne vulgaris. Arch Dermatol Res. 2011;303(1):19-27.
18. 18. Wang B, He YL. Association of the TNF-α gene promoter polymorphisms at nucleotide -238 and -308 with acne susceptibility: a meta-analysis. Clin Exp Dermatol. 2019;44(2):176-83.
19. 19. Schmeling H, Wagner U, Peterson A, Horneff G. Tumor necrosis factor alpha promoter polymorphisms in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2006;24(1):103-8.
20. 20. Kaabachi S, Kaabachi W, Rafrafi A et al. Tumor necrosis factor gene polymorphisms in Tunisian patients with non-small cell lung cancer. Clin Lab. 2013;59(11-12):1389-95.
21. 21. Philpott MP, Sanders DA, Bowen J, Kealey T. Effects of interleukins, colony-stimulating factor and tumour necrosis factor on human hair follicle growth in vitro, a possible role for interleukin-1 and tumour necrosis factor alpha in alopecia areata. Br J Dermatol. 1996;135:942-48.
22. 22. Gohary YM, Abdel Fattah DS. Detection of Tumor Necrosis Factor-alpha in Nonlesional Tissues of Alopecia Areata Patients: A Prove for a Systemic Disease. Int J Trichology. 2017;9(4):154-9.
23. 23. Abdel Halim D, Abu Zeid OM, Rashed L, Saleh MA. Alteration of serum and tissue tumor necrosis factor alpha levels: A possible mechanism of action of oral pulse steroids in the treatment of alopecia areata. J Cosmet Dermatol. 2019;8(4):1128-32.