TGFB1 (rs1800470 and rs1800469) variants are independently associated with disease activity and autoantibodies in rheumatoid arthritis patients

• Published in: Clinical and experimental medicine 2022-02, Vol.22 (1), p.37-45
• Main Authors: Iriyoda, Tatiana Mayumi Veiga, Flauzino, Tamires, Costa, Neide Tomimura, Lozovoy, Marcell Alysson Batisti, Reiche, Edna Maria Vissoci, Simão, Andréa Name Colado
• Format: Article
• Language: English
• Subjects: Alleles; Arthritis, Rheumatoid - genetics; Autoantibodies; Citrulline; Genotypes; Genotyping; Haplotypes; Hematology; Humans; Internal Medicine; Joint diseases; Medicine; Medicine & Public Health; Oncology; Original Article; Plasma levels; Remission; Rheumatoid arthritis; Rheumatoid factor; Rheumatoid Factor - genetics; Transforming Growth Factor beta1 - genetics; Transforming growth factor-b1
• ISSN: 1591-8890; 1591-9528
• DOI: 10.1007/s10238-021-00725-9

To evaluate the association between TGFB1  + 869 T > C (rs1800470) and TGFB1- 509 C > T (rs1800469) variants with susceptibility for rheumatoid arthritis (RA), disease activity, presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and TGF- β 1 plasma levels. A total of 262 patients with RA and 168 control individuals were tested for the TGFB1 variants using a TaqMan genotyping assay. Disease activity score in 28 joints (DAS28) classified RA patients into two groups of disease activity: remission/mild (DAS28  C and −509 C > T variants, independently or in haplotype combination, were not associated with RA’s susceptibility. Patients with the TGFB1- 509 TT genotype had a higher frequency of DAS28 ≥ 3.2 (OR 2.58, 95% CI 1.04–6.42, p  = 0.041). The TGFB1  + 869 CC genotype in seropositive patients for RF or anti-CCP was associated with decreased TGF- β 1 levels ( p  = 0.032 and p  = 0.039, respectively). Patients with the TGFB1  + 869 C allele and elevated RF titles demonstrated a higher frequency of DAS28 ≥ 3.2 ( p  = 0.037). The TGFB1  + 869 T > C variant was associated with diminished TGF- β 1 plasma levels and moderate/severe activity disease only in seropositive RF patients. This is the first study showing that TGF-β1 plasma levels can be modulated by the interaction between the TGFB1  + 869 T > C variant and autoantibodies. However, the TGFB1- 509 C > T variant was associated with moderate/severe activity disease, independently of autoantibodies positivity. Thus, our findings suggest that TGFB1  + 869 T > C and −509 C > T variants can predict activity disease in different RA patient subgroups.