IL10 gene polymorphisms are associated with asthma phenotypes in children

Abstract

IL10 is an anti-inflammatory cytokine that has been found to have lower production in macrophages and mononuclear cells from asthmatics. Since reduced IL10 levels may influence the severity of asthma phenotypes, we examined IL10 single-nucleotide polymorphisms (SNPs) for association with asthma severity and allergy phenotypes as quantitative traits. Utilizing DNA samples from 518 Caucasian asthmatic children from the Childhood Asthma Management Program (CAMP) and their parents, we genotyped six IL10 SNPs: 3 in the promoter, 2 in introns, and one in the 3′ UTR. Using family-based association tests, each SNP was tested for association with asthma and allergy phenotypes individually. Population-based association analysis was performed with each SNP locus, the promoter haplotypes and the 6-loci haplotypes. The 3′ UTR SNP was significantly associated with FEV 1 as a percent of predicted (FEV 1 PP) (P=0.0002) in both the family and population analyses. The promoter haplotype GCC was positively associated with IgE levels and FEV 1 PP (P=0.007 and 0.012, respectively). The promoter haplotype ATA was negatively associated with lnPC 20 and FEV 1 PP (P=0.008 and 0.043, respectively). Polymorphisms in IL10 are associated with asthma phenotypes in this cohort. Further studies of variation in the IL10 gene may help elucidate the mechanism of asthma development in children. Keywordsinterleukin 10 (IL10); single nucleotide polymorphism (SNP); genetic association; family-based association test (FBAT); haplotype; promoter; 3′; untranslated region (3′UTR)

Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a

“…Half life of IL10 mRNA in normal melanocytes is much shorter than in melanoma cell lines (7). Also, genetic variations in the 3Ј UTR of IL10 have been shown to be associated with IL-10 levels that could lead to disease pathogenesis (8,9). Therefore, a pellucid understanding of the posttranscriptional regulation of IL10 will be of scientific and clinical significance.…”

MicroRNA-466l Upregulates IL-10 Expression in TLR-Triggered Macrophages by Antagonizing RNA-Binding Protein Tristetraprolin-Mediated IL-10 mRNA Degradation

“…miR-106a can bind the IL-10 39UTR and regulate its expression posttranscriptionally (36). Besides, genetic variations in the IL-10 39UTR has been shown to be associated with IL-10 levels that could lead to disease pathogenesis (37,38). Therefore, a full understanding of the posttranscriptional regulation of IL-10 expression will be of scientific and clinical significance.…”

Differential interleukin-10 production stratified by −571 promoter polymorphism in purified human immune cells

“…We demonstrated that the A allele was associated with elevated total serum IgE in subjects heterozygotic or homozygotic for this base exchange [20]. In addition, this polymorphism has also been linked with increased severity of a number of diseases including asthma, rheumatoid arthritis, systemic lupus erythromatosus (SLE) and inflammatory bowel disease [21][22][23][24], and is associated with changes in tumorigenesis and transplantation tolerance [25] and rapid progression to AIDS in individuals infected with HIV [26]. Each of these represents immune diseases that predictably could be associated with a loss of either tolerance or repression of immune responses.…”