title: 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.
authors: 1 Department of Pediatrics, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea , Pucheon-Si, Korea.
authors: Jin-Soon
authors: JS
authors: Suh
authors: Seong H
authors: SH
authors: Cho
authors: Joo-Ho
authors: JH
authors: Chung
authors: Ahrim
authors: A
authors: Moon
authors: Yong-Koo
authors: YK
authors: Park
authors: Byoung-Soo
authors: BS
authors: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D018123:Receptors, Interleukin; C415369:interleukin-22 receptor
references: Cytokine Growth Factor Rev. 2010 Oct;21(5):353-63
references: 20864382
references: Hepatology. 2004 May;39(5):1332-42
references: 15122762
references: Nat Genet. 2000 Nov;26(3):354-7
references: 11062479
references: Clin Immunol. 2008 Nov;129(2):277-85
references: 18771958
references: J Am Soc Nephrol. 2007 Aug;18(8):2408-15
references: 17634434
references: Clin Immunol. 2012 May;143(2):116-27
references: 22459704
references: Cytokine Growth Factor Rev. 2006 Oct;17(5):367-80
references: 17030002
references: Nat Genet. 2011 Mar 13;43(4):321-7
references: 21399633
references: Laryngoscope. 2007 Oct;117(10):1839-43
references: 17906500
references: Otolaryngol Head Neck Surg. 2009 May;140(5):741-7
references: 19393422
references: Annu Rev Immunol. 2011;29:71-109
references: 21166540
references: Bioinformatics. 2006 Aug 1;22(15):1928-9
references: 16720584
references: Eur J Pediatr. 2011 Apr;170(4):503-9
references: 20953797
references: Biochem Biophys Res Commun. 2008 Sep 26;374(3):448-53
references: 18639518
references: Nephron. 2002 Mar;90(3):320-7
references: 11867953
references: Cytokine Growth Factor Rev. 2010 Oct;21(5):365-79
references: 20870448
references: Nat Med. 2008 Mar;14(3):275-81
references: 18264110
references: Nat Genet. 2011 Dec 25;44(2):178-82
references: 22197929
references: Am J Hum Genet. 2006 Dec;79(6):1130-4
references: 17186473
references: Nat Rev Nephrol. 2012 Mar 20;8(5):275-83
references: 22430056
references: Science. 2002 Jun 21;296(5576):2225-9
references: 12029063
references: J Biol Chem. 2002 Mar 1;277(9):7341-7
references: 11706020
references: J Immunol. 2007 Feb 15;178(4):2229-40
references: 17277128
references: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9511-6
references: 11481447
references: Cytokine. 2008 Jan;41(1):16-23
references: 18061474
references: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G827-38
references: 16537974
references: J Mol Med (Berl). 2009 May;87(5):523-36
references: 19330474
references: J Am Soc Nephrol. 2008 Dec;19(12):2384-95
references: 18776126
references: Eur J Immunol. 2006 May;36(5):1309-23
references: 16619290
references: Curr Opin Nephrol Hypertens. 2011 Mar;20(2):153-60
references: 21301336
references: Nephrol Dial Transplant. 2005 Feb;20(2):342-8
references: 15618239
references: Immunity. 2004 Aug;21(2):241-54
references: 15308104
references: J Clin Pathol. 2011 Oct;64(10):893-7
references: 21725041
references: J Nephrol. 2010 Nov-Dec;23(6):626-32
references: 20383870
references: Nephrol Dial Transplant. 2001 Feb;16(2):269-75
references: 11158399