Interleukin-10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands.
The purpose of this study was to examine whether several allelic variants in the polymorphic interleukin (IL)-10 promoter region were related with an increased risk of developing systemic lupus erythematosus (SLE) in Spanish patients from Canary Islands. Microsatellites (MS) at positions -4000 and -1200 (IL10R and IL10G, respectively) and single nucleotide polymorphisms (SNPs) (MS) at positions -1082G/A, -819C/T and -592C/A of the IL-10 promoter were analysed in patients with SLE and healthy controls from Canary Islands (Spain). We found that SNPs but not MS were associated with SLE. The GCC haplotype frequency was significantly higher in SLE patients (0.43) than in healthy donors (0.33) [P = 0.02; OR = 1.50 (95% CI = 1.06-2.14)], whereas the ACC haplotype was less represented in patients (0.28 vs. 0.37) [P = 0.02; OR = 0.64 (95% CI = 0.44-0.92)]. To assess the functional role of genotypes, serum IL-10 levels from patients and controls were quantified by ELISA. Also, the lipopolysaccharide-induced IL-10 secretion by monocytes from healthy controls was evaluated in vitro. Serum IL-10 levels were higher in patients [median (interquartile range) = 2.8 pg/mL (1.8-4.2)] than in controls [0.9 pg/mL (0-3.5)] (P = 0.02), but no association was observed between serum IL-10 levels or lipopolysaccharide-induced IL-10 secretion and the IL-10 promoter haplotypes. These data suggest that the IL-10 promoter haplotype that produces higher levels of cytokine is associated with SLE in patients from Canary Islands.
Rosado
S
S
Fundacion LAIR, Madrid, Spain, and Sevicio de Medicina Interna I, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Rua-Figueroa
I
I
Vargas
J A
JA
Garcia-Laorden
M I
MI
Losada-Fernandez
I
I
Martin-Donaire
T
T
Perez-Chacon
G
G
Rodriguez-Gallego
C
C
Naranjo-Hernandez
A
A
Ojeda-Bruno
S
S
Citores
M J
MJ
Perez-Aciego
P
P
D000483:Alleles; D002478:Cells, Cultured; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D009000:Monocytes / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013030:Spain
D008070:Lipopolysaccharides; D016753:Interleukin-10