Interleukin‐10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands

Abstract

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.

Association of extended interleukin-10 promoter haplotypes with disease susceptibility and manifestations in German patients with systemic lupus erythematosus

“…[31][32][33] Several investigators have studied the association of these polymorphisms and their haplotypes with susceptibility to SLE in populations from different ethnic origin (for review see Lopez et al 34 ). The results are inconsistent, as GCC was found to be increased in Spanish SLE patients, 35 whereas other authors did not confirm this finding. The low IL-10 producing ATA haplotype was found to be associated with neuropsychiatric lupus and renal disease in Dutch and Chinese populations.…”

Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

“…Different alleles and haplotypes of these polymorphisms have been reported to be associated with SLE susceptibility both in Caucasian [18-20] as well as in Asiatic [21-23] populations and several studies also revealed the association of these polymorphisms with various clinical manifestations in SLE patients: discoid lesions [24], neurological manifestations development [21, 25], and anti-DNA [26], anti-Smith [27] and anti-cardiolipin antibodies production [21]. We can hypothesize that an abnormal production of IL-10 may cause exacerbated autoantibodies release and inflammatory processes establishment, which may favor SLE and its manifestations incidence.…”

IL-10 and TNFαGenotypes in SLE

“…However, in spite of the considerable number of genetic studies performed, no definitive result about its involvement in SLE susceptibility was achieved. Some works showed significant associations between IL-10 microsatellites or SNPs with SLE susceptibility or with the development of certain clinical or immunological features, while other studies indicated that these polymorphisms did not appear to have any relevance in the disease (Table 2) [27–31, 34, 45, 59–71]. With respect to microsatellite variants, different alleles of IL10.G have been reported to be associated with SLE incidence in various populations.…”