ANALYSIS OF HAND ECZEMA DEVELOPMENT DEPENDING ON GLUCOCORTICOID RECEPTOR GENE BclI POLYMORPHISM

Methkal A. M., Kuts L. V.

MEDICAL GENETICS

Scentific article

Hand eczema is one of the most common chronic inflammatory skin and socially significant diseases which negatively affects the life quality and leads to disability and economic burden on society. The pathogenesis of hand eczema is multifactorial. Numerous studies indicate the complex nature of disorders from many body systems in patients with eczema, but the leading role belongs to genetically determined or acquired immune disorders. The glucocorticoid receptor plays an important regulatory role in the immune system and the development of many immune-dependent diseases. Since the differences in GR sensitivity may affect the effector immune functions and the development of immune-dependent diseases, the aim of this study was to determine whether there is a relationship between the development of hand eczema and BclI single nucleotide polymorphism of the glucocorticoid receptor gene. The venous blood of 143 patients with hand eczema (42% of women and 58% of men) age of (42.2 ± 11.1) years was used in the study. The control group was consisted of 97 people (50.5% women and 49.5% men) age of (43.8 ± 11.5) years. Single nucleotide polymorphism BclI (reference number – rs41423247) of the glucocorticoid receptor gene GR (NR3C1) was determined by the method described previously (Fleury et al. 2003). Statistical analysis was performed using the program SPSS 22.0. Quantitative variables were tested for normal distribution by the Shapiro-Wilk method. The comparisons of the means between the two groups were performed using Student’s t-test for independent samples. The frequency comparison of different indicators distribution between the control and the group of patients was performed using the Pearson’s test. Binary logistic regression was used to analyze the relationship between BclI polymorphism and the occurrence of hand eczema in different models. The P value <0.05 was considered significant. Thus, there was found that a statistically significant relationship exists in the dominant model (P = 0.016) during the study of the association between the development of hand eczema and NR3C1 gene BclI polymorphism. The risk of hand eczema in carriers of the minor allele G is 1.95 times higher (CI 95 % = 1.13 – 3.37) than in homozygotes of main allele. The association of BclI single nucleotide polymorphism with the occurrence of eczema under the recessive and superdominant model was not detected (P > 0.05).

BclI polymorphism, glucocorticoid receptor, hand eczema.

1. Antonov D, Schliemann S, Elsner P. Hand dermatitis: a review of clinical features, prevention and treatment. Am J Clin Dermatol. 2015;16:257-70.
2. Meding B, Jarvholm B. Incidence of hand eczema-a population-based retrospective study. J Invest Dermatol. 2004;122:873-7.
3. Lerbaek A, Kyvik KO, Ravn H, Menne T, Agner T. Incidence of hand eczema in a population-based twin cohort: genetic and environmental risk factors. Br J Dermatol. 2007;157:552-7.
4. Thyssen JP, Johansen JD, Linneberg A, Menne T. The epidemiology of hand eczema in the general population-prevalence and main findings. Contact Dermatitis. 2010;62:75-87.
5. Gronhagen CM, Liden C, Bergstrom A, Kull I, Wahlgren CF, Meding B. Prevalence and incidence of hand eczema in adolescence: report from BAMSE–a population-based birth cohort. Br J Dermatol. 2014;171:609-14.
6. Coenraads PJ. Hand eczema. N Engl J Med. 2012;367:1829-37.
7. Sonja Molin. Pathogenese des Handekzems. Der Hautarzt. 2019;70:755-9. Available from: doi.org/10.1007/s00105-019-04474-5
8. Kaae J, Menné T, Carlsen BC, Zachariae C, Thyssen JP. The hands in health and disease of individuals with filaggrin lossoffunction mutations: clinical reflections on the hand eczema phenotype. Contact Dermatitis. 2012;67(3):119-24.
9. Arushanyan EB, Al’-Absi DzhM, Chebotarev VV. Lechebnye vozmozhnosti melatonina i ego vliyanie na immunologicheskie pokazateli u bol’nyh ekzemoj. Eksperim. i klin. farmakol. 2003;66(3):59-61. [in Russian].
10. Bіlovol AM. Kompensatornі reakcіі pri ekzemі: ocіnka gіsterezisu іmunnih rozladіv. Vrachebnaya praktika. 2005;1:63-70. [in Ukrainian].
11. Manon JM van Oosten, Radboud JEM Dolhain, Jan W Koper, Elisabeth FC van Rossum. Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Research & Therapy. 2010;12:R159.
12. Diepgen TL, Andersen KE, Chosidow O, Coenraads PJ. Guidelines for diagnosis, prevention and treatment of hand eczema. J Deutsche Dermatologische Gesellschaft (DDG). 2014;1610:3-79. DOI: 10.1111/ddg.12510
13. Fleury I, Beaulieu P, Primeau M, Labuda D, Sinnett D, Krajinovic M. Characterization of the BclI Polymorphism in the Glucocorticoid Receptor Gene. Clinical Chemistry. 2003;49(9):1528-32.
14. van Rossum EF, Koper JW, van den Beld AW, Uitterlinden AG, Arp P, Ester W, et al. Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol (Oxf). 2003;59:585-92.
15. Panek M, Pietras T, Szemraj J, Kuna P. Association analysis of the glucocorticoid receptor gene (NR3C1) haplotypes (ER22/23EK, N363S, BclI) with mood and anxiety disorders in patients with asthma. Experimental and therapeutic medicine. 2014;8:662-70. DOI: 10.3892/etm.2014.1734
16. Manenschijn L, van den Akker EL, Lamberts SW, van Rossum EF. Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann N Y Acad Sci. 2009;1179:179-98.
17. van Moorsel D, van Greevenbroek MM, Schaper NC, Henry RM, Geelen CC, van Rossum EF, et al. BclI glucocorticoid receptor polymorphism in relation to cardiovascular variables: the Hoorn and CODAM studies. Eur J Endocrinol. 2015;173:455-64.
18. Zhdanova MV, Bogdanova MA, Vojtovich AN, Ashchepkova OM. Osobennosti techeniya bronhial’noj astmy u detej s razlichnymi genotipami BclI polimorfizma gena glyukokortikoidnogo receptora. Pediatriya. 2007;86(4):19-24. [in Russian].
19. Kostik MM, Baranov DN, Kozyreva AA, Glazkov PB, Shcheplyagina LA, Larionova VI. Klinicheskoe znachenie BclI-polimorfizma gena glyukokortikoidnogo receptora u detej s yuvenil’nym idiopaticheskim artritom. Voprosy prakt. pediatrii. 2008;6(3):8-11. [in Russian].
20. Vozіanova SV, Gorovenko NG, Bojko VV, Rossoha ZІ. Analіz pokaznikіv stupenya tyazhkostі dicgіdrotichnoі ekzemi dolon’ і stop z urahuvannyam іndeksu DASI, shkali ocіnki HECSI ta polіmorfіzmu C646G za genom NR3C1. Dermatologіya ta venerologіya. 2017;4(78):21-5. [in Ukrainian].

«Bulletin of problems biology and medicine» Issue 3 (157), 2020 year, 174-177 pages, index UDK 616.5-002.2-616.5-002.158.091

10.29254/2077-4214-2020-3-157-174-177