Abstract
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 (χ27 = 48.97, P = 0.001, Caucasians; and χ27 =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.
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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).
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Linker-Israeli, M., Wallace, D., Prehn, J. et al. Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression. Genes Immun 1, 45–52 (1999). https://doi.org/10.1038/sj.gene.6363631
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DOI: https://doi.org/10.1038/sj.gene.6363631
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