AB0009 ASSOCIATION OF STAT4 RS7574865, RUNX1 RS9979383, IL6 RS1800795, IL6R RS2228145, IL6R RS4845618 WITH SYSTEMIC LUPUS ERYTHEMATOSUS SUSCEPTIBILITY AND SOME LUPUS MANIFESTATIONS IN BELARUSIAN POPULATION
Authors: N. Dostanko, V. Yagur, R. Goncharova, E. Siniauskaya, T. Zybalova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic lupus erythematosus (SLE) has a significant genetic predisposition. Many genetic variants of susceptibility to SLE have been published and analyzed, but the clinical and functional significance of the various genotypes has not yet been clearly defined [1]. Objectives: To estimate the association between some of non-HLA gene polymorphisms such as STAT4 rs7574865, RUNX1 rs9979383, IL6 rs1800795, IL6R rs2228145, IL6R rs4845618 and susceptibility to SLE in Belarusian population as well as some disease manifestations. Methods: We examined 383 healthy blood donors and 54 SLE patients (18-72 years old, median age 35) classified according to the 1997 American College of Rheumatology (ACR) revised classification criteria [2]. Deoxyribonucleic acid was extracted from peripheral blood samples by phenol-chloroform method. Genotyping was performed by real-time PCR with fluorescent probes. Differences of distribution of all the single nucleotide polymorphism (SNP) genotypes and their associations with secondary antiphospholipid syndrom (APS) and lupus arthritis were analyzed using Pearson χ 2 (χ 2 ) and two-way Fisher exact test (F, p 2-t ). Diagnostic odds ratio (dOR), likelihood ratio of positive (LR + ) and negative (LR – ) tests and corresponding 95% confidence intervals (CI) were also calculated. Results: We revealed significant difference in STAT4 rs7574865 genotypes in SLE patients and healthy donors (χ 2 =8,27, р=0,016) with significant increase of ТТ genotype frequency in SLE patients vs healthy donors (χ 2 =6.83 p=0.009; p 2-t =0.020; dOR=3.78 (CI 95% 1.36-10.55); LR + =3.44 (CI 95% 1.35-8.71); LR – =0.91 (CI 95% 0.83-0.98)). Lupus arthritis was more common in risk TT-genotype SLE carriers than in other SLE patients (χ 2 =5.902 p=0.015; p 2-t =0.027). We revealed significant increase of СТ genotype (RUNX1 rs9979383) in healthy donors vs SLE patients (χ 2 =4.14; p=0.042; dOR=0.53 (CI 95% 0.29-0.98); LR + =0.69 (CI 95% 0.45-0.99); LR – =1.3 (CI 95% 1.01-1,56)). Lupus arthritis was more common in SLE СТ-genotype carriers than in other SLE patients (χ 2 =4.66 p=0.031; p 2-t =0.058). Significant differences in IL6 rs1800795, IL6R rs2228145 and IL6R rs4845618 genotypes distribution between studied groups were not found (χ 2 , p=0.427, p=0.559 and p=0.407, correspondingly) but GG-genotype (IL6 rs1800795) carriership in SLE patients was associated with increased APS frequency (χ 2 =4.45, p=0.035; dOR=0.19 (CI 95% 0.04-0.9); LR + =0.28 (CI 95% 0.07-0.93); LR – =1.41 (CI 95% 1.03-1.64). Conclusion: Our data suggest the susceptibility to SLE in ТТ genotype of STAT4 rs7574865 polymorphism, protective role of СТ genotype of RUNX1 rs9979383 for SLE and association between GG-genotype of IL6 rs1800795 and APS in SLE patients in Belarusian population. Lupus arthritis was associated with ТТ genotype of STAT4 rs7574865 and СТ genotype of RUNX1 rs9979383. References: [1]Chen L, Morris DL, Vyse TJ. Genetic advances in systemic lupus erythematosus: an update. Curr Opin Rheumatol 2017;29:423–33. [2]Hochberg MC. Updating the American College of Rheumatology Revised Criteria for the classification of Systemic Lupus Erythematosus. Arthritis Rheum 1997;40:1725. Disclosure of Interests: None declared