The frequency of distribution of the genotypes of the IL4 polymorphism (rs 2243250) in psoriasis and psoriatic arthritis

Psoriasis (PS) and psoriatic arthritis (PsA) are multifactorial diseases determined by the result of complex combined interaction of genetic and environmental factors. The study of genetic polymorphism of PS and PsA will allow identification of common diagnostic criteria for the progression of pathology. The aim was to analyze the frequency of distribution of genotypes of the promoter region of the C-590T (rs2243250) gene IL4 in patients with psoriasis and psoriatic. The study included patients with psoriasis (n = 49) and psoriatic arthritis (n = 48), which, taking into account the carriage of certain genotypes, are divided into groups: 1, PS, carriers of the C/С genotype (n = 31); 2, PS, carriers of the C/T and T/T genotype (n = 18); 3, PsA, carriers of the C/С genotype (n = 30); and 4, PsA, carriers of the C/T and T/T genotype (n = 18). DNA extraction from whole venous blood was performed using a standard kit with a sorbent. Genotyping allelic variants was carried out by the method of restriction analysis of amplification products (RFLP-analysis) of specific regions of the genome. In PS carriers of the C/С IL4 (rs2243250), the value of the PASI index is statistically significantly lower relative to the carriers of the C/T and T/T genotypes. A possible association of the carriage of the C/T and T/T genotypes in PsA with nail psoriasis was noted in comparison with the C/C genotype. When studying intergroup differences, it was determined that the carriage of the C/C genotype in PsA can influence the clinical course of the psoriatic process with frequent exacerbations and involvement of more than 30 % of the hairy part in the pathological process. The carriage of the C/T and T/T genotypes in PsA may be associated with the Koebner phenomenon and the metabolic disorders in comparison with PS. Differences in the carriage of the C/C genotypes relative to C/T and T/T IL4 (rs2243250) in psoriasis and psoriatic arthritis were determined. Given the extremely low number of patient groups, the results should be considered as preliminary and require further testing on much larger samples.

psoriasis, psoriatic arthritis, genes polymorphism, cytokines, IL4

1. Smolnikova M.V., Smirnova S.V. Genetic factors in the immunopathogenesis of psoriasis and psoriatic arthritis. Meditsinskaya Immunologiya = Medical Immunology. 2014;16(3):211-220. (in Russian)

2. Khairutdinov V.R. Genetic profile of psoriasis patients. Vestnik Dermatologii i Venerologii = Journal of Dermatology and Venereology. 2011;4:14-19. (in Russian)

3. Bidwell J.L., Wood N.A., Morse H.R., Olomolaiye O.O., Keen L.J., Laundy G.J. Human cytokine gene nucleotide sequence alignments: supplement 1. Eur. J. Immunogenet. 1999;26(2-3):135-223.

4. Cantagrel A., Navaux F., Loubet-Lescoulié P., Nourhashemi F., Enault G., Abbal M., Constantin A., Laroche M., Mazières B. Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis. Arthritis Rheum. 1999;42(6):10931100. DOI 10.1002/1529-0131(199906)42:63.0.CO;2-P.

5. Chiesa Fuxench Z.C., Shin D.B., Ogdie Beatty A., Gelfand J.M. The risk of cancer in patients with psoriasis: a population-based cohort study in the health improvement network. JAMA Dermatol. 2016;152:282-290. DOI 10.1001/jamadermatol.2015.4847.

6. de Vlam K., Gottlieb A.B., Mease P.J. Current concepts in psoriatic arthritis: pathogenesis and management. Acta Derm. Venereol. 2014; 94(6):627-634. DOI 10.2340/00015555-1833.

7. Feld J., Nissan S., Eder L., Rahat M.A., Elias M., Rimar D., Laor A., Bitterman H., Zisman D. Increased prevalence of metabolic syndrome and adipocytokine levels in a psoriatic arthritis cohort. J. Clin. Rheumatol. 2018;24(6):302-307. DOI 10.1097/RHU.0000000000000721.

8. Gelfand J.M., Neimann A.L., Shin D.B., Wang X., Margolis D.J., Troxel A.B. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296:1735-1741. DOI 10.1001/jama.296.14.1735.

9. Indhumathi S., Rajappa M., Chandrashekar L., Ananthanarayanan P.H., Thappa D.M., Negi V.S. T helper-2 cytokine/regulatory T-cell gene polymorphisms and their relation with risk of psoriasis in a South Indian Tamil cohort. Hum. Immunol. 2017;78(2):209-215. DOI 10.1016/j.humimm.2016.12.006.

10. Kim Y.K., Pyo C.W., Choi H.B., Kim S.Y., Kim T.Y., Kim T.G. Associations of IL-2 and IL-4 gene polymorphisms with psoriasis in the Korean population. J. Dermatol. Sci. 2007;48(2):133-139. DOI 10.1016/j.jdermsci.2007.06.014.

11. Konenkov V.I., Prokofiev V.F., Shevchenko A.V., Golovanova O.V., Smolnikova M.V. Polymorphism of immune response genes as a factor of predisposition to disease development. Russ. J. Immunol. 2001;6(2):123-130.

12. Kurd S.K., Troxel A.B., Crits-Christoph P., Gelfand J.M. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch. Dermatol. 2010;146(8):891-895. DOI 10.1001/archdermatol.2010.186.

13. Munir S., ber Rahman S., Rehman S., Saba N., Ahmad W., Nilsson S., Mazhar K., Naluai A.T. Association analysis of GWAS and candidate gene loci in a Pakistani population with psoriasis. Mol. Immunol. 2015;64(1):190-194. DOI 10.1016/j.molimm.2014.11.015.

14. Naldi L. Epidemiology of psoriasis. Curr. Drug Targets Inflamm. Allergy. 2004;3:121-128. O’Rielly D.D., Rahman P. Where do we stand with the genetics of psoriatic arthritis? Curr. Rheumatol. Rep. 2010;12(4):300-308. DOI 10.1007/s11926-010-0111-4.

15. Szepietowski J.C., Reich A. Pruritus in psoriasis: An update. Eur. J. Pain. 2016;20(1):41-46. DOI 10.1002/ejp.768.

16. Thrum S. Obesity and autoimmunity: Adipose tissue as an immune organ? Z. Rheumatol. 2017;76(4):348-350. DOI 10.1007/s00393017-0298-0.

17. Truong B., Rich-Garg N., Ehst B.D., Deodhar A.A., Ku J.H., VakilGilani K., Danve A., Blauvelt A. Demographics, clinical disease characteristics, and quality of life in a large cohort of psoriasis patients with and without psoriatic arthritis. Clin. Cosmet. Investig. Dermatol. 2015;8:563-569. DOI 10.2147/CCID.S90270.

18. Wan J., Wang S., Haynes K., Denburg M.R., Shin D.B., Gelfand J.M. Risk of moderate to advanced kidney disease in patients with psoriasis: population based cohort study. BMJ. 2013;347:f5961. DOI 10.1136/bmj.f5961.

19. Zargari O., Leyli E.K., Azimi S.Z. Nail involvement in patients with psoriatic arthritis in Northern Iran. Autoimmune Dis. 2018;4608490. DOI 10.1155/2018/4608490.