RT Journal Article
SR Electronic
T1 Interleukin 6 Gene Polymorphisms Are Associated with Systemic Lupus Erythematosus in Koreans
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 2251
OP 2258
DO 10.3899/jrheum.100170
VO 37
IS 11
A1 JA-YOUNG JEON
A1 HYOUN-AH KIM
A1 SEUNG-HYUN KIM
A1 HAE-SIM PARK
A1 CHANG-HEE SUH
YR 2010
UL http://www.jrheum.org/content/37/11/2251.abstract
AB 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 polymorphisms (SNP; −572 C > G, −278 A > C in the promoter, and 330 T > G, and 334 A > T in exon 2) and a −373 AnTn tract polymorphism in the IL-6 gene. The genotype frequency, −373 A10T11, −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 (CA10T11ATA, 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 polymorphisms are associated with disease susceptibility and phenotype of SLE. In addition, promoter polymorphisms may be involved in regulation of IL-6 expression.