Single-nucleotide polymorphisms of transforming growth factor-beta1 gene in Taiwanese patients with systemic lupus erythematosus.
Transforming growth factor-beta1 (TGF-beta1) is involved in the generation of CD8+ T suppressor cells, natural killer (NK) cells and regulatory T (Th3) cells for down-regulatory effects on antibody production. We studied TGF-beta1 activity in patients with systemic lupus erythematosus (SLE) to try to clarify whether the dysregulation by TGF-beta1 is genetically determined. Sera from 55 patients with clinically inactive SLE, who were taking minimal steroids and/or hydroxychloroquine, and 40 healthy controls, along with supernatants from concanavalin A-stimulated peripheral blood mononuclear cell (PBMC) cultures from 18 patients with SLE and 10 controls were subjected to TGF-beta1 enzyme-linked immunosorbent assay. A total of 138 patients with SLE and 182 controls were genotyped for 5 single-nucleotide polymorphisms (SNPs) of TGF-beta1: -988C/A, -800G/A, -509C/T, Leu10/Pro10 and Arg25/Pro25. Patients with SLE had lower serum levels of TGF-beta1 compared with controls (p=0.052). The unstimulated and stimulated TGF-beta1 production of PBMCs in patients with SLE was higher than in controls, although these differences did not reach significance (p=0.073 and 0.074, respectively). None of the TGF-beta1 SNPs was strongly associated with SLE in Taiwanese patients or had any prognostic significance in lupus nephritis. Hence these polymorphisms do not represent a genetic predisposition to SLE. The intrinsic capability of immunoregulation for spontaneous B cell hyperactivity through PBMC TGF-beta1 production was presumed to be intact in clinically stable SLE in Taiwanese. Whether the lower serum TGF-beta1 level that causes the defective immune regulation in SLE is primarily under genetic control or secondary to the influence of ongoing cellular interactions in the cytokine context needs to be elucidated.
Lu
Ling-Ying
LY
Division of Allergy, Immunology, and Rheumatology, Veterans General Hospital-Kaohsiung, Taiwan, ROC.
Cheng
He-Hsiung
HH
Sung
Ping-Kuang
PK
Yeh
Jeng-Jung
JJ
Shiue
Yow-Ling
YL
Chen
Angela
A
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1