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 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 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).


CONCLUSIONS
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.
Jeon
Ja-Young
JY
Ajou University School of Medicine, Department of Allergy and Rheumatology, and BK21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Woncheon-dong, San5, Youngtong-gu, Suwon, Republic of Korea 443-721.
Kim
Hyoun-Ah
HA
Kim
Seung-Hyun
SH
Park
Hae-Sim
HS
Suh
Chang-Hee
CH
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D015850:Interleukin-6