Single-nucleotide polymorphisms of transforming growth factor-?1 gene in Taiwanese patients with systemic lupus erythematosus

Ling-Ying Lu¹, He-Hsiung Cheng¹, Ping-Kuang Sung¹, Jeng-Jung Yeh², Yow-Ling Shiue², Angela Chen^2
1Division of Allergy, Immunology, and Rheumatology, Veterans General Hospital-Kaohsiung; and ²Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC

Received: September 12, 2003 Revised: November 12, 2003 Accepted: November 20, 2003

Corresponding author: Angela Chen, PhD, National Sun Yat-Sen University, P.O. Box 59-69, Kaohsiung, Taiwan 80424, ROC. E-mail:

Transforming growth factor-?1 (TGF-?1) 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-?1 activity in patients with systemic lupus erythematosus (SLE) to try to clarify whether the dysregulation by TGF-?1is 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-?1 enzyme-linked immunosorbent assay. A total of 138 patients with SLE and 182 controls were genotyped for 5 single-nucleotide polymorphisms (SNPs) of TGF-?1: -988C/A, -800G/A, -509C/T, Leu¹⁰/Pro¹⁰ and Arg²⁵/Pro²⁵. Patients with SLE had lower serum levels of TGF-?1compared with controls (p=0.052). The unstimulated and stimulated TGF-?1 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-?1 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-?1 production was presumed to be intact in clinically stable SLE in Taiwanese. Whether the lower serum TGF-?1 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.

Key words: Case-control studies, single nucleotide polymorphism, systemic lupus erythematosus, transforming growth factor beta

J Microbiol Immunol Infect 2004;37:145-152.