Interleukin 6 Gene Polymorphisms Are Associated with Systemic Lupus Erythematosus in Koreans

Objective. Interleukin 6 (IL-6) gene polymorphisms are known to play a role in chronic inflammatory disorders. We searched for polymorphisms in the IL-6 gene and described their pathogenic role in Korean patients with systemic lupus erythematosus (SLE). Methods. Genomic DNA was extracted from 151 patients with SLE and 151 controls, and about 1.4 kb-sized IL-6 genes located between promoter region and exon 2 region were amplified by polymerase chain reaction. The promoter activity was analyzed by luciferase reporter assay in Hep3B cells and HeLa cells. Results. We identified 4 single-nucleotide polymorphism (SNP; -572 C > G, -278 A > C in the promoter, and 330 T > G, and 334 A > T in exon 2) and a -373 A(n)T(n) tract polymorphism in the IL-6 gene. The genotype frequency, -373 A(10)T(11), -278 C. and 334 T allele were significantly associated with SLE (p < 0.001, p = 0.03 and p = 0.005, respectively). Patients with SLE carrying the -572 G allele had anti-dsDNA more frequently (p = 0.007). In addition, thrombocytopenia was significantly more common in patients carrying the -278 C allele (p = 0.006). In the haplotype analysis, patients with SLE had more frequently haplotype HT3 (CA(10)T(11)ATA, dominant model, p = 0.012) that was associated with arthritis, leukopenia, anti-dsDNA, and hypocomplementemia. Promoter reporter structures carrying the -278 C allele displayed significantly higher promoter activity than the 278 A allele in Hep3B cells (p < 0.001) and HeLa cells (p < 0.001). Conclusion. These data suggest that IL-6 gene polymorphism are associated with disease susceptibility and phenotype of SLE. In addition, promoter polymorphisms may be involved in regulation of IL-6 expression. (First Release Sept 152010; J Rheumatol 2010;37:2251-8; doi:10.3899/jrheum.100170)