Agnieszka Paradowska-Gorycka1, Magdalena Roszak2, Barbara Stypinska3, Anna Lutkowska4, Marcela Walczyk5, Marzena Olesinska5, Anna Wajda3, Piotr Piotrowski6, Mariusz Puszczewicz7, Dominik Majewski7, Pawel Piotr Jagodzinski4. 1. Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. paradowska_aga@interia.pl. 2. Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland. 3. Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. 4. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland. 5. Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. 6. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan; and Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. 7. Department of Rheumatology and Internal Diseases, Poznan University of Medical Science, Poznan, Poland.
Abstract
OBJECTIVES: The aim of the study was to explore whether TGF-β and IL-6 gene polymorphisms may be associated with SLE and assess the frequency of HLA-DRB1 alleles in Polish systemic lupus erythematosus (SLE) patients. METHODS: 216 SLE patients and 552 healthy individuals were examined for TGF-β rs1800469 and rs1800470 by TaqMan SNP genotyping assay and for and IL-6(rs2069827 and rs1800795 using the PCR- RFLP method. RESULTS: An increased frequency of TT genotype and T allele of the TGF β -509 C/T was found in SLE patients (p=0.02). The TGF-β 869 C allele was more frequent in SLE patients. The genotype-phenotype analysis showed association between the TGF β -509 C/T and mean value of CRP, ESR, haemoglobin, APTT, Pt and INR (p=0.05, p=0.03, p<0.001, p=0.03, p=0.03 and p=0.05, respectively) as well as anti-SSA and anti-Sm presence (p=0.04 and p=0.03, respectively); the TGF- β 869 T/C and mean value of APTT and INR (p=0.01 and p=0.05, respectively); the IL-6 -174 G/C and SLICC (p=0.05), anti-SSA (p=0.05) and anti-SSB (p=0.05). A higher TGF-β and IL-6 serum level were found in SLE patients compared to controls (both p<0.0001). In SLE patients with the TGF-β -509 TT genotype have shown positive association with the TGF-β serum levels. Polish SLE patients have strong positive association with HLA-DRB1*52.1, and negative with the HLA-DRB1*07:01 allele. HLA-DRB1*52.1 was also associated with higher TGF-β serum levels in the Polish population. CONCLUSIONS: Our results suggested that the TGF β -509 C/T variant may be considered as a genetic marker for SLE in the Polish population.
OBJECTIVES: The aim of the study was to explore whether TGF-β and IL-6 gene polymorphisms may be associated with SLE and assess the frequency of HLA-DRB1 alleles in Polish systemic lupus erythematosus (SLE) patients. METHODS: 216 SLEpatients and 552 healthy individuals were examined for TGF-β rs1800469 and rs1800470 by TaqMan SNP genotyping assay and for and IL-6(rs2069827 and rs1800795 using the PCR- RFLP method. RESULTS: An increased frequency of TT genotype and T allele of the TGF β -509 C/T was found in SLEpatients (p=0.02). The TGF-β 869 C allele was more frequent in SLEpatients. The genotype-phenotype analysis showed association between the TGF β -509 C/T and mean value of CRP, ESR, haemoglobin, APTT, Pt and INR (p=0.05, p=0.03, p<0.001, p=0.03, p=0.03 and p=0.05, respectively) as well as anti-SSA and anti-Sm presence (p=0.04 and p=0.03, respectively); the TGF- β 869 T/C and mean value of APTT and INR (p=0.01 and p=0.05, respectively); the IL-6 -174 G/C and SLICC (p=0.05), anti-SSA (p=0.05) and anti-SSB (p=0.05). A higher TGF-β and IL-6 serum level were found in SLEpatients compared to controls (both p<0.0001). In SLEpatients with the TGF-β -509 TT genotype have shown positive association with the TGF-β serum levels. Polish SLEpatients have strong positive association with HLA-DRB1*52.1, and negative with the HLA-DRB1*07:01 allele. HLA-DRB1*52.1 was also associated with higher TGF-β serum levels in the Polish population. CONCLUSIONS: Our results suggested that the TGF β -509 C/T variant may be considered as a genetic marker for SLE in the Polish population.