Single nucleotide polymorphism T869C of transforming growth factor-beta 1 gene and systemic lupus erythematosus: association with disease susceptibility and lupus nephritis.

Transforming growth factor β1 (TGF-β1) has a large role in the control of autoimmunity. Single nucleotide polymorphisms (SNP) in the promoter of TGF-β1 cytokine gene are known to alter the production of this important cytokine. Decreased levels of TGF-β1 may contribute to systemic lupus erythematosus (SLE) susceptibility, activity and organ damage. Lupus nephritis (LN) occurs in more than one-third of patients with SLE. In this study we measured serum levels of TGF-β1 and assessed TGF-β1 single nucloetide polymorphism (SNP) at codon 10 (T869C) in Egyptian SLE population in order to verify whether there is a relationship between this polymorphism, serum level of TGF-β1, SLE susceptibility, clinical manifestations and lupus nephritis. We studied 56 consecutive SLE female patients and 40 healthy female volunteers as control group. Serum levels of TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA) and the polymorphism of the TGF-β1 gene, T869C was analyzed using the method of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The genotype and allele frequencies of T869C of the TGF-β1 gene did not differ between SLE patients and healthy controls. Serum levels of TGF-β1 were significantly reduced in patients with SLE as compared with levels in healthy controls (P < 0.001). The genotype and allele frequencies of T869C of the TGF-β1 gene did not differ between SLE patients with lupus nephritis (LN) and SLE patients without LN. Lower levels of TGF-β1 were found in patients with LN than in patients without LN. TGF-β1 was significantly decreased in TT group than in CC and TC groups (P < 0.001). No significant correlation was found between serum TGF-β1 level, SLEDAI scores and clinical manifestations. In conclusion, these results suggest that T869C polymorphism of the TGF-β1 gene is not associated with SLE disease susceptibility and specific clinical manifestations. However, this polymorphism may lead to the production of low serum level of TGF-β1 especially with TT genotype and consequently plays an important role in the development of renal damage.