AB0010 ASSOCIATION OF SOME NON-HLA GENE POLYMORPHISMS WITH SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS IN WOMEN IN BELARUSIAN POPULATION

Abstract

BackgroundDespite the recent progress in our understanding of the genetic predisposition to systemic lupus erythematosus (SLE) its clinical and functional significance is not fully clarified yet and needs to be implemented in personalized care [1].ObjectivesTo estimate the association between some single nucleotide polymorphisms (SNPs) of 9 non-HLA genes-candidates as STAT4 rs7574865, PTPN2 rs2542151, PTPN22 rs2476601, AGER rs1035798, TRAF1/C5 rs3761847, SLC7A11 rs13128867, RUNX1 rs9979383, IL6 rs1800795, IL6R rs2228145, IL6R rs4845618 and susceptibility to SLE in Belarusian women for the following predictive model development.MethodsWe examined 316 women: among them 59 SLE patients (mean age 39.84, CI95% 36.62-43.06) classified according to the 1997 American College of Rheumatology (ACR) revised classification criteria and 257 age-matched healthy controls (blood donors, mean age 38.12, 95% confidence interval (CI95%) 36.77-39.46). Deoxyribonucleic acid was extracted from peripheral blood samples by phenol-chloroform method. Genotyping was performed by real-time PCR with fluorescent probes. Descriptive analysis, test for Hardy–Weinberg equilibrium, multiple inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive) for single SNPs, Akaike information criteria (AIC) and Bayesian information criteria (BIC) were analyzed using SNPStats web tool [2]. Pearson χ 2 (χ 2), two-way Fisher exact test (F, p 2-t), odds ratio (OR), likelihood ratio of positive (LR +) and negative (LR –) tests with corresponding CI95% were also calculated.ResultsExact test for all genotype frequencies distribution of all studied SNPs didn’t reveal significant differences with Hardy-Weinberg equilibrium in all controls and SLE groups. We noted significant increase of minor ТТ genotype frequency of STAT4 rs7574865 in SLE vs healthy women with recessive inheritance model as the best-fitting one according to its less AIC and BIC values (OR=3.78 (CI95% 1.35-10.62); p=0.016; LR + =3.45 (CI95% 1.37-8.60); LR – =0.91 (CI95% 0.84-0.98)). We revealed protection of minor A allele of AGER rs1035798 carriership with log-additive model of inheritance as the best-fitting one according to AIC and BIC values against SLE development in women (OR=0.52 (CI95% 0.33-0.83); p=0.004; LR + =0.70 (CI95% 0.50-0.93); LR – =1.47 (CI95% 1.10-1.86)). We also noted significant increase of minor allele G frequency of TRAF1/C5 rs3761847 in SLE vs healthy women with dominant inheritance model (OR=3.61 (CI95% 1.05-12.38); p=0.019; LR + =1.30 (CI95% 1.03-1.43); LR – =0.36 (CI95% 0.12-0.92)) and increase of AA genotype frequency in healthy women (p 2-t =0.041). We revealed that minor allele G of PTPN2 rs2542151 is more frequent in SLE women vs healthy controls and has overdominant model of inheritance (OR=1.98 (CI95% 1.09-3.59); p=0.026; LR + =1.57 (CI95% 1.07-2.20); LR – =0.79 (CI95% 0.62-0.97)).There were no significant differences in genotypes and alleles distribution for PTPN22 rs2476601, RUNX1 rs9979383, SLC7A11 rs13128867 and IL6 rs1800795 in studied population and we noted only non-significant tendency in minor SNP genotypes distribution of IL6R rs4845618 and IL6R rs2228145 between healthy controls and women with SLE.ConclusionOur data suggest the susceptibility to SLE in women with ТТ genotype of STAT4 rs7574865 polymorphism and allele G carriers of both TRAF1/C5 rs3761847 and PTPN2 rs2542151 as well as protective role of AGER rs1035798 A allele carriership againt SLE development in women of Belarusian population.