¹Departments Medicine, The Cedars-Sinai Medical Center, Burns & Allen Research Institute, UCLA School of Medicine, Los Angeles, CA 90048, USA

²Medical Genetics, The Cedars-Sinai Medical Center, Burns & Allen Research Institute, UCLA School of Medicine, Los Angeles, CA 90048, USA

³Brigham and Women's Hospital, Boston, MA 02115, USA

Correspondence to: Dr M Linker-Israeli, Ceders-Sinai Medical Center, D-5073, 8700 Berverly Boulevard, Los Angeles, CA 90048, USA

These studies were supported in part by NIH/NIAMS AR 42520, The Arthritis National Research Foundation, The American Lupus Society (MLI) and The Arthritis Foundation/Southern California Chapter (JRK).

To evaluate the association of alleles of regions having regulatory potential in the IL-6 gene, with SLE, the AT-rich minisatellite in the 3' flanking region and the 5' promoter-enhancer of the IL-6 gene were genotyped by PCR- and RFLP-based methods. The AT-rich minisatellite allele distribution pattern was significantly different in SLE (n = 146) as compared to 139 controls (²₇ = 48.97, P = 0.001, Caucasians; and ²₇ =19.93, P = 0.006, African-Americans). In either race, short allele sizes (792 bp) were seen exclusively in SLE patients (P = 0.001), whereas the 828-bp allele was over-represented in controls (P = 0.015 and 0.002). In contrast, there was no preferential association of SLE with G/C alleles in the 5' region of the IL-6 gene. Furthermore, our results suggest that the 3' minisatellite alleles have biological significance: (1) B lymphoblastoid cells of patients having one or two SLE-associated alleles secreted IL-6 in 3- to 4-fold higher levels than non-allelic cells (P < 0.05); (2) higher percentages (approximately 4-fold) of il-6 positive monocytes were observed in individuals having sle-associated il-6 alleles; (3) in lupus patients having sle-associated minisatellite alleles, il-6 mrna stability was significantly enhanced.

IL-6 alleles; SLE; lupus; minisatellites; cytokine alleles