Interleukin-10 Promoter Polymorphism in Psoriasis

Abstract

Beneficial effects of interleukin-10 therapy and lower endogenous interleukin-10 formation compared with atopic dermatitis and cutaneous T cell lymphomas indicated that interleukin-10 is a key cytokine in psoriasis. The interleukin-10 promoter is highly polymorphic, with two informative microsatellites, interleukin-10.G and interleukin-10.R. In order to understand whether interleukin-10 itself is a predisposing gene for the psoriasis susceptibility we analyzed interleukin-10 promotor polymorphism in patients. The distribution of interleukin-10.G and interleukin10.R microsatellite alleles did not vary between patients (n = 78) and healthy controls (n = 80). In addition, when the psoriasis patients were stratified according to age of onset (younger than 40 y of age, or age 40 and older), no difference in allele distribution was observed; however, a clear differential distribution was revealed at the interleukin10.G locus when patients were stratified according to whether they had a positive family history of psoriasis (p = 0.04). This difference was due to an over-representation of the interleukin10.G13 allele in those patients with familial disease (40.4% vs 19.6%, Chi-square = 7.292, p = 0.007). The positive association of allele interleukin10.G13 with familial psoriasis was especially true when patients with an early onset (< 40 y of age) of the disease were compared with those patients with early onset against a nonfamilial background (39.6% vs 14.5%, Chi-square = 8.959, p = 0.003). Patients with age-of-onset of less than 40 were 4-fold [odds ratio = 3.85 (1.55--9.62)] more likely to have a psoriatic family background if they carried this interleukin10.G13 allele. These data suggest that the interleukin-10 locus contributes to the heritability of psoriasis susceptibility.

IL10 gene polymorphisms are associated with asthma phenotypes in children

“…Eleven SNPs Lazarus et al, 2002] and two microsatellite (AC) n repeats have been reported in the promoter [Eskdale and Gallagher, 1995;Kube et al, 1995;Eskdale et al, 1996Eskdale et al, , 1997. Three promoter SNPs at -1,082, -819, and -592 (corresponding to SNP numbers -1117A/G, -854C/T, and -627C/A in our analysis) have been shown by several groups to form three common haplotypes in Caucasian populations: GCC, ACC, and ATA Eskdale et al, 1999;Asadullah et al, 2001;Helminen et al, 2001]. Promoter association studies with these three haplotypes have shown significant association in inflammatory diseases such as lupus erythematosus, psoriasis, and multiple sclerosis Asadullah et al, 2001;Myhr et al, 2002].…”

“…Three promoter SNPs at -1,082, -819, and -592 (corresponding to SNP numbers -1117A/G, -854C/T, and -627C/A in our analysis) have been shown by several groups to form three common haplotypes in Caucasian populations: GCC, ACC, and ATA Eskdale et al, 1999;Asadullah et al, 2001;Helminen et al, 2001]. Promoter association studies with these three haplotypes have shown significant association in inflammatory diseases such as lupus erythematosus, psoriasis, and multiple sclerosis Asadullah et al, 2001;Myhr et al, 2002]. Variation at the -592 site has also been associated with increased risk of HIV-1 infection and disease progression [Shin et al, 2000].…”

Polymorphisms in the interleukin-20 gene: relationships to plaque-type psoriasis

“…[13][14][15][16] Previous studies have presented evidence for an association between IL-10 SNPs with susceptibility to a number of autoimmune, malignant, and infectious diseases. Until now, the only study by Asadullah et al 17 have proved definitely that the IL-10 locus contributes to the susceptibility to psoriasis. In the present study, possible associations between IL-20 polymorphisms and psoriasis were assessed.…”

Psoriasis: genetic associations and immune system changes

“…A polymorphic microsatellite in the IL-10 promoter also revealed evidence for association with psoriasis in patients with a family history of disease. 97 Protective effects conferred by some alleles and haplotypes within this cluster of genes has also been proposed, along with suggestions that some alleles influence severity or clinical course of disease. 98,99 A comprehensive association analysis of alleles and haplotypes within this cluster of genes is warranted in other patient populations.…”