A Polymorphism of Interleukin-22 Receptor Alpha-1 Is Associated with the Development of Childhood IgA Nephropathy

Abstract

Recent studies suggest that dysregulated innate immunity plays an important role in the pathogenesis of immunoglobulin A nephropathy (IgAN). The interleukin-20 subfamily and its receptor, interleukin-22 receptor alpha-1 (IL-22R1), were recently identified as immunomodulators in human diseases, acting as mediators of mucosal host defense. However, the potential role of IL-22R1 in the pathogenesis of IgAN has not been explored. In the current study, 194 patients with IgAN and 287 normal controls were genotyped for coding polymorphisms of the IL-22R1 gene and the association between the polymorphisms and IgAN was investigated. Local expression of IL-22R1 was examined in patients with IgAN and healthy controls using immunohistochemistry. Our case-control analysis showed that genotypes of rs3795299 were associated with childhood IgAN. Individuals with the CC genotype of rs3795299 had about 3-fold reduced risk of IgAN compared with those with the GG genotype in the codominant model (P=0.0028) and those with the genotypes containing the G allele (GG or GC) in the recessive model (P=0.002). After Bonferroni correction, the association between the rs3795299 CC genotype and reduced risk of developing IgAN remained significant. Furthermore, the renal expression of IL-22R1 was significantly higher in healthy controls compared with subjects with IgAN. Our data suggest that the CC genotype of rs3795299 polymorphism in the IL-22R1 gene is associated with the reduced risk of IgAN, and this genetic association was supported by the higher renal expression of IL-22R1 in healthy controls compared with patients with IgAN.

Association between the AGTR1 A1166C polymorphism and risk of IgA nephropathy: a meta-analysis

“…A family history of chronic nephritis, susceptibility to the common cold, preference for salty foods, frequent consumption of raw eggs, and a high intake of carbohydrates, including rice, are significantly associated with increased IgAN risk (Wakai et al, 1999). In addition, many reports have indicated that certain genetic polymorphisms are associated with susceptibility to this disease (Suh et al, 2013;Zhou et al, 2013).…”

Genetic Variants in Interleukin Genes and Susceptibility to IgA Nephropathy: A Meta-Analysis

“…The titles and abstracts of all articles were reviewed and 204 were excluded; full texts and data integrity were then reviewed and another 45 articles were excluded. Finally, seven clinical case-control studies were included in this meta-analysis (Lim et al, 2002;Syrjanen et al, 2002;Chin et al, 2005;Bao et al, 2007;Wang et al, 2008;Hahn et al, 2009;Suh et al, 2013). Publication years of the eligible studies ranged from 2002 to 2013.…”

“…Previous studies have demonstrated immunogenetic factors play a fundamental role in the progression of IgAN through immune defense, metabolism, and immune surveillance (Wada et al, 2003;Berthoux et al, 2011). Recently, several clinical studies have confirmed that genetic variants of immune genes might increase the risk of IgAN (Chin et al, 2005;Suh et al, 2013).…”

“…Therefore, it is biologically plausible that genetic variants in IL genes might play an important role in the development and progression of IgAN (Hahn et al, 2009). Recent studies have indicated that genetic variants of IL genes might be significantly associated with the risk of IgAN (Chin et al, 2005;Suh et al, 2013). However, there is also some evidence that IL genetic variants had no effect on susceptibility to IgAN (Syrjanen et al, 2002;Bao et al, 2007;Hahn et al, 2009).…”

Association ofT869, C509T, G915Cgene polymorphism of transforming growth factor-β1 with IgA nephropathy risk

“…Current evidence indicates that gene polymorphism of some genes are associated with the susceptibility of IgAN. [3][4][5] The factor of gene polymorphism is one of the most important factors which take part in the etiology of some diseases. The evidence from meta-analysis might be powerful compared with the individual investigation.…”