TGFB1 +869 T > C (rs1800470) variant is independently associated with susceptibility, laboratory activity, and TGF-β1 in patients with systemic lupus erythematosus

Abstract

The aim of this study was to evaluate the association of the +869 T > C (rs1800470) and −509 C > T (rs1800469) TGFB1 variants, individually or in haplotypes structure, with susceptibility, autoantibodies, disease activity, and TGF-β1 plasma levels in patients with systemic lupus erythematosus (SLE). The study included 203 patients with SLE and 165 healthy controls. TGFB1 variants were determined by real-time polymerase chain reaction (qPCR). Plasma levels of TGF-β1 were determined using immunofluorimetric assay. The TGFB1 + 869 CC genotype was associated with SLE susceptibility (OR: 1.710, 95%CI: 1.020–2.866, p = 0.042) and with reduction of C4 (p = 0.040) and TGF-β1 levels (p = 0.044). In addition, patients with TGFB1 + 869 TC and CC genotypes and positive anti-dsDNA had lower TGF-β1 levels than those with TT (p = 0.004). TGFB1 −509 TT genotype was associated with reduced levels of C4 (p = 0.032). There was no association between haplotypes and clinical and laboratory parameters. Our data demonstrated that the TGFB1 + 869 T > C variant could be used as a genetic marker for SLE susceptibility and both variants as predictors of laboratory activity. This is the first study to demonstrate that TGF-β1 levels could be modulated by the interaction between TGFB1 + 869 C allele, in homozygosity, or heterozygosity, and the presence of anti-dsDNA.

Keywords:

• Systemic lupus erythematosus
• transforming growth factor-beta 1
• rs1800470
• rs18004469
• SLEDAI

Ethical approval

This study was conducted after approval by the Institutional Research Ethics Committees of the University of Londrina, Paraná, Brazil (CAAE: 01865212.0.0000.5231). All procedures performed in this study involving human participants were according to the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Author contributions

Conception and research design: Andréa Name Colado Simão, Tamires Flauzino, Nicole Perugini Stadtlober; Manuscript writing and discussion of results: Andréa Name Colado Simão; Edna Maria Vissoci Reiche; Nicole Perugini Stadtlober; Tamires Flauzino; Data collection: Nicole Perugini Stadtlober, Lorena Flor da Rosa Franchi Santos, Tatiana Mayumi Veiga Iriyoda, Neide Tomimura Costa which contributed equally; Laboratory analysis: Nicole Perugini Stadtlober, Tamires Flauzino, Lorena Flor da Rosa Franchi Santos, Marcell Alysson Batisti Lozovoy; Statistical analysis: Andréa Name Colado Simão, Tamires Flauzino. All authors have read and approved the final manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

The study was supported by grants from Coordination for the Improvement of Higher Level of Education Personnel (CAPES) and Institutional Program for Scientific Initiation Scholarship (PIBIC) of The National Council for Scientific and Technological Development (CNPq).