Role of the Promoter Polymorphism IL-6 −174G/C in Dermatomyositis and Systemic Lupus Erythematosus

Abstract

The promoter polymorphism −174G/C within the interleukin-6 gene (IL-6) has been reported to have a functional importance through the modulation of IL-6 gene expression in vitro and in vivo. IL-6 is thought to play an important role in autoimmune diseases and the effect of its receptor inhibitor—tocilizumab—has been recently studied. The aim of this case-control study was to investigate the association between the interleukin-6 −174G/C single nucleotide polymorphism and the susceptibility to dermatomyositis (DM) and systemic lupus erythematosus (SLE) in Bulgarian patients. Altogether, 87 patients—52 with SLE and 35 with DM—as well as 80 unrelated healthy controls were included in this study. All of them were analyzed by restriction fragment length polymorphism analysis (RFLP). The GG genotype and the G allele appeared to be associated with SLE, especially in women. None of the genotypes showed an association with DM. However, the G allele appeared to be associated with muscle weakness and it is a risk factor for elevated muscle enzymes. Our results indicate that IL-6 −174G/C polymorphism might be associated with the susceptibility to SLE especially in women. Although it is not associated with DM, it seems that IL-6 −174G/C polymorphism could modulate some clinical features in the autoimmune myopathies.

Association of the interleukin-6 polymorphisms with systemic lupus erythematosus: a meta-analysis

“…Six studies in all investigated the association of the IL-6-174 G/C polymorphism with clinical and laboratory characteristics (malar rash, discoid skin lesions, photosensitivity, oral ulcer, arthritis, serositis, nephritis, neurological disorder, haematological disorder, haematological compromise, central nervous system disease, thrombocytopenia, anti-double stranded (ds)DNA, anti-Ro, anti-La, anti-Sm, anti-histones, anticardiolipin and anti-β 2 -glycoprotein antibodies). 13,19–23 The results of association between this polymorphism and discoid skin lesions or renal disease remain controversial, while other association was not statistically significant in these six studies. Therefore, a meta-analysis was carried out to evaluate the association of the IL-6-174 G/C polymorphism with discoid skin lesions and renal disease.…”

“…Four studies describe the association between this polymorphism and discoid skin lesions or renal disease. 13,19,21,23 However, the Schotte study did not provide the number of genotype distributions of patients negative for the features. 19 The Asano study only provided the genotype data under a recessive model.…”

The Effects of Gene Polymorphisms in Interleukin-4 and Interleukin-6 on the Susceptibility of Rheumatoid Arthritis in a Chinese Population

“…IL-6 is another multifunctional B-cell differentiation cytokine, which also plays important role in inducing the final maturation of activated B cells into immunoglobulin-secreting plasma cells and influencing the susceptibility of RA [ 7 , 8 , 11 , 22 – 24 ], dermatomyositis and systemic lupus erythematosus [ 39 ], liver cirrhosis and hepatocellular carcinoma [ 40 ], diabetic microvascular complications [ 41 ], coronary heart disease [ 42 ], acute appendicitis [ 43 ], and so on. Although the association of IL-6-174 G/C with RA was well studied in many populations, such as Europeans, Turkish, Koreans, and Egyptians, besides a very preliminary study in a few Han population in Guangdong, studies about the association of IL-6-174 G/C with RA in Chinese population do not be reported.…”

Role of the IL-6 Gene in the Etiopathogenesis of Idiopathic Scoliosis

“…IL-6 (-174 C/G) is involved in the pathogenesis of some autoimmune disorders. Hristova et al [ 6 ] reported a statistically significant association between IL-6 -174G allele and systemic lupus erythematosus in Bulgarian population.…”