Interleukin 18 receptor 1 gene polymorphisms are associated with asthma

Abstract

The interleukin 18 receptor (IL18R1) gene is a strong candidate gene for asthma. It has been implicated in the pathophysiology of asthma and maps to an asthma susceptibility locus on chromosome 2q12. The possibility of association between polymorphisms in IL18R1 and asthma was examined by genotyping seven SNPs in 294, 342 and 100 families from Denmark, United Kingdom and Norway and conducting family-based association analyses for asthma, atopic asthma and bronchial hyper-reactivity (BHR) phenotypes. Three SNPs in IL18R1 were associated with asthma (0.01131rPr0.01377), five with atopic asthma (0.00066rPr0.00405) and two with BHR (0.01450rPr0.03203) in the Danish population; two SNPs were associated with atopic asthma (0.00397rPr0.01481) and four with BHR (0.00435rPr0.03544) in the UK population; four SNPs showed associations with asthma (0.00015rPr0.03062), two with atopic asthma (0.01269rPr0.04042) and three with BHR (0.00259rPr0.01401) in the Norwegian population; five SNPs showed associations with asthma (0.00005rPr0.03744), five with atopic asthma (0.00001rPr0.04491) and three with BHR (0.03568rPr0.04778) in the combined population. Three intronic SNPs (rs1420099, rs1362348 and rs1974675) showed replicated association for at least one asthma-related phenotype. These results demonstrate significant association between polymorphisms in IL18R1 and asthma.

Proapoptotic IL-18 in patients with chronic hepatitis C treated with pegylated interferon-alpha

“…Indeed, a protective effect of IL-18 has been shown in mouse models of herpes simplex virus infection, vaccinia virus infection, hepatitis B virus and human immunodeficiency virus type 1 infection [8][9][10]. Moreover increased IL-18 activation has been implicated in the pathogenesis of various autoimmune disorders, and due to its inflammatory properties, this cytokine could potentially also contribute to the inappropriate and harmful immune activation in HCVinfected patients [11,12]. Therefore, the exact role of IL-18 in the pathogenesis of HCV infection is at present unclear.…”

Interleukin-18 and interleukin-18 receptor- expression in allergic asthma

“…Recently, an IL-18 gene polymorphism was reported to be associated with asthma severity and higher serum IL-18 levels: the rs5744247 variant, which has higher transcriptional activity than the wildtype allele [4]. In addition, the IL-18 receptor (IL-18R) gene (on 2q21) has been identified as a candidate gene associated with increased susceptibility to asthma in children [5], and polymorphisms of the gene have been associated with allergic asthma and airway hyperresponsiveness (AHR) [6]. We have evaluated serum levels of IL-18 and the expression of IL-18Ra, as well as other Th2-associated cytokines, in stable allergic asthmatic subjects, compared with allergic nonasthmatic subjects and healthy controls.…”

Single nucleotide polymorphism (rs1035130C>T) in the interleukin 18 receptor 1 gene and susceptibility to severe <i>P. falciparum</i> malaria in Lafia, North-central Nigeria

“…Nature 526: 207-211. the association of the rs1035130 polymorphism with malaria, there are studies showing association of this Bidwell, J., Keen, L., Gallagher, G., Kimberly, R., SNP with inflammatory diseases including asthma and Huizinga, T., McDermott, M. F., Oksenberg, J., atopic dermatitis (Reijmerink et al, 2008;Zhu et al, McNicholl, J., Pociot, F., Hardt, C., and D'Alfonso, S. 2008), and inflammatory bowel disease (Zhernakova (1999). Cytokine gene polymorphism in human et al., 2008).…”

“…Few studies have shown association of this However, their expression and production is SNP with diseases, particularly inflammatory diseases essentially controlled by genetic factors, especially including asthma and atopic dermatitis (Reijmerink et single nucleotide polymorphisms (SNPs) within al., 2008;Zhu et al, 2008). There is however, paucity coding and regulatory regions of cytokine-expressing of data on the association of this polymorphism with genes (Bidwell et al, 1999).…”