Interleukin 7 receptor gene polymorphisms and haplotypes are associated with susceptibility to IgA nephropathy in Korean children

Hahn,Won-Ho; Suh,Jin-Soon; Park,Hae-Jung; Cho,Byoung-Soo

doi:10.3892/etm.2011.322

Interleukin 7 receptor gene polymorphisms and haplotypes are associated with susceptibility to IgA nephropathy in Korean children

Authors:
- Won-Ho Hahn
- Jin-Soon Suh
- Hae-Jung Park
- Byoung-Soo Cho
View Affiliations

Affiliations: Department of Pediatrics, East West Kidney Diseases Research Institute, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea, Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
Published online on: July 21, 2011 https://doi.org/10.3892/etm.2011.322
Pages: 1121-1126

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

An abnormal T-cell response is involved in the pathogenesis of various renal diseases. Survival of naïve T cells is dependent on interleukin 7 (IL7) and its receptor (IL7R). Thus, we investigated the association between IL7R single nucleotide polymorphisms (SNPs) and childhood IgA nephropathy (IgAN). We analyzed the genotypic distributions of two missense SNPs of IL7R, rs1494558 (Ile66Thr) and rs1494555 (Val138Ile), among 198 pediatric IgAN patients and 288 healthy controls. Haplotype analysis and measurement of pair-wise linkage disequilibrium were performed. In addition, the genotypes of patient subgroups, determined by the presence of nephrotic range proteinuria (>40 mg/m2/h) and pathological advancement, were analyzed. The genotyping data of IgAN patients and controls showed significant differences in rs1494558 (codominant, P=0.0003; dominant, P=0.0003) and rs1494555 (codominant, P=0.0038; dominant, P=0.0099). In the haplotype analysis, AC (codominant, P=0.0066) and GT (codominant, P=0.0005; dominant, P=0.0006) were significantly associated with susceptibility to IgAN. Furthermore, in the analysis of clinical subgroups of IgAN patients, rs1494558 was associated with nephrotic range proteinuria (codominant, P=0.027; recessive, P=0.023). Our results suggest that IL7R may be associated with disease susceptibility and proteinuria in childhood IgAN.

View Figures

View References

1	Coppo R: Pediatric IgA nephropathy: clinical and therapeutic perspectives. Semin Nephrol. 28:18–26. 2008. View Article : Google Scholar
2	Alexopoulos E, Seron D, Hartley RB, Nolasco F and Cameron JS: The role of interstitial infiltrates in IgA nephropathy: a study with monoclonal antibodies. Nephrol Dial Transplant. 4:187–195. 1989.PubMed/NCBI
3	Nikolic-Paterson DJ and Atkins RC: The role of macrophages in glomerulonephritis. Nephrol Dial Transplant. 16(Suppl 5): 3–7. 2001. View Article : Google Scholar
4	Fry TJ and Mackall CL: Interleukin-7: from bench to clinic. Blood. 99:3892–3904. 2002. View Article : Google Scholar : PubMed/NCBI
5	Ye SK, Maki K, Kitamura T, et al: Induction of germline transcription in the TCRgamma locus by Stat5: implications for accessibility control by the IL-7 receptor. Immunity. 11:213–223. 1999. View Article : Google Scholar : PubMed/NCBI
6	Gregory SG, Schmidt S, Seth P, et al: Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet. 39:1083–1091. 2007. View Article : Google Scholar : PubMed/NCBI
7	Van Roon JA, Glaudemans KA, Bijlsma JW and Lafeber FP: Interleukin 7 stimulates tumour necrosis factor alpha and Th1 cytokine production in joints of patients with rheumatoid arthritis. Ann Rheum Dis. 62:113–119. 2003.PubMed/NCBI
8	Cox SN, Sallustio F, Serino G, et al: Altered modulation of WNT-beta-catenin and PI3K/Akt pathways in IgA nephropathy. Kidney Int. 78:396–407. 2010. View Article : Google Scholar : PubMed/NCBI
9	Goetz CA, Harmon IR, O'Neil JJ, Burchill MA and Farrar MA: STAT5 activation underlies IL7 receptor-dependent B cell development. J Immunol. 172:4770–4778. 2004. View Article : Google Scholar : PubMed/NCBI
10	Sun LY, Zhang HY, Feng XB, Hou YY, Lu LW and Fan LM: Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 16:121–128. 2007. View Article : Google Scholar : PubMed/NCBI
11	Van Roon JA, Hartgring SA, Wenting-van Wijk M, et al: Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha blockade in patients with rheumatoid arthritis. Ann Rheum Dis. 66:664–669. 2007.PubMed/NCBI
12	Van Roon JA and Lafeber FP: Role of interleukin-7 in degenerative and inflammatory joint diseases. Arthritis Res Ther. 10:1072008.PubMed/NCBI
13	Maruyama K, Yoshida M, Nishio H, et al: Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy. Pediatr Nephrol. 16:350–355. 2001. View Article : Google Scholar : PubMed/NCBI
14	Nakanishi K, Sako M, Yata N, et al: A-20C angiotensinogen gene polymorphism and proteinuria in childhood IgA nephropathy. Pediatr Nephrol. 19:144–147. 2004. View Article : Google Scholar : PubMed/NCBI
15	Lee HS, Lee MS, Lee SM, et al: Histological grading of IgA nephropathy predicting renal outcome: revisiting H.S. Lee's glomerular grading system. Nephrol Dial Transplant. 20:342–348. 2005.PubMed/NCBI
16	Sole X, Guino E, Valls J, Iniesta R and Moreno V: SNPStats: a web tool for the analysis of association studies. Bioinformatics. 22:1928–1929. 2006. View Article : Google Scholar : PubMed/NCBI
17	Stephens M, Smith NJ and Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 68:978–989. 2001. View Article : Google Scholar : PubMed/NCBI
18	Gabriel SB, Schaffner SF, Nguyen H, et al: The structure of haplotype blocks in the human genome. Science. 296:2225–2229. 2002. View Article : Google Scholar : PubMed/NCBI
19	Long D, Blake S, Song XY, Lark M and Loeser RF: Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13. Arthritis Res Ther. 10:R232008. View Article : Google Scholar : PubMed/NCBI
20	Mobini R, Andersson BA, Erjefalt J, et al: A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 receptor in allergic inflammation. BMC Syst Biol. 3:192009. View Article : Google Scholar
21	Lundmark F, Duvefelt K, Iacobaeus E, et al: Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet. 39:1108–1113. 2007. View Article : Google Scholar : PubMed/NCBI
22	Booth DR, Arthur AT, Teutsch SM, et al: Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis. J Mol Med. 83:822–830. 2005. View Article : Google Scholar : PubMed/NCBI
23	Hoppenbrouwers IA, Aulchenko YS, Janssens AC, et al: Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis. J Hum Genet. 54:676–680. 2009. View Article : Google Scholar : PubMed/NCBI
24	Heron M, Grutters JC, van Moorsel CH, et al: Variation in IL7R predisposes to sarcoid inflammation. Genes Immun. 10:647–653. 2009. View Article : Google Scholar : PubMed/NCBI
25	Santiago JL, Alizadeh BZ, Martinez A, et al: Study of the association between the CAPSL-IL7R locus and type 1 diabetes. Diabetologia. 51:1653–1658. 2008. View Article : Google Scholar : PubMed/NCBI