Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression.
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 (chi 2(7) = 48.97, P = 0.001, Caucasians; and chi 2(7) = 19.93, P = 0.006, African-Americans). In either race, short allele sizes (< or = 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.
Linker-Israeli
M
M
Department Medicine, Cedars-Sinai Medical Center, Burns & Allen Research Institute, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Wallace
D J
DJ
Prehn
J
J
Michael
D
D
Honda
M
M
Taylor
K D
KD
Paul-Labrador
M
M
Fischel-Ghodsian
N
N
Fraser
P A
PA
Klinenberg
J R
JR
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D015850:Interleukin-6; D012333:RNA, Messenger