Association of the paired box 2 gene polymorphism with the susceptibility and pathogenesis of Henoch‑Schönlein purpura in children

Chen,Jing; Fang,Xiangling; Dang,Xiqiang; Wu,Xiaochuan; Yi,Zhuwen

doi:10.3892/mmr.2014.2908

Association of the paired box 2 gene polymorphism with the susceptibility and pathogenesis of Henoch‑Schönlein purpura in children

Authors:
- Jing Chen
- Xiangling Fang
- Xiqiang Dang
- Xiaochuan Wu
- Zhuwen Yi
View Affiliations

Affiliations: Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Paediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: November 10, 2014 https://doi.org/10.3892/mmr.2014.2908
Pages: 1997-2003

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

The present study aimed to investigate the distribution of paired box 2 (PAX2) gene polymorphisms in healthy populations and in patients with Henoch‑Schönlein purpura (HSP), focusing on the association between PAX2 gene polymorphisms and the susceptibility and clinical characteristics of HSP. Genomic DNA was extracted from the peripheral venous blood of 100 healthy children (mean age: 5±1.9 years) and 118 children with HSP (mean age: 10.2±2.3 years). Polymerase chain reaction (PCR) was used to amplify exons 1‑12 of the PAX2 gene. Denaturing high performance liquid chromatography and DNA sequencing analysis were conducted for screening of mutations in the PAX2 gene in the PCR products. No genetic polymorphism of the PAX2 gene was identified in exons 1‑7, 9, 10 or 12. Two single nucleotide polymorphisms (SNPs), which presented as complete linkage haplotype 798C>T/909A>C, were identified in exon 8. An SNP (1164T>A) was also identified in exon 11. No significant difference in the allele and genotype frequency distribution of exon 8 (798C>T) or 11 (1164T>A) of the PAX2 gene was identified between the HSP and control groups (P>0.05). However, the frequency of the PAX2 heterozygous genotype 798C>T in the HSP with nephritis (HSPN) group was significantly higher than those in the controls and in the HSP without nephritis group (P<0.05). Furthermore, no significant correlation was identified between the PAX2 gene exon 8 polymorphism (798 C>T) and the renal pathology of children with HSPN. An SNP (1164T>A) was identified in exon 11. The PAX2 heterozygous genotype 798C>T did not increase susceptibility to HSP, however, it may be used clinically as a screening indicator for HSP in children with a high risk of renal involvement.

View Figures

View References

1	Li L, Zhang J, Zhang Y and Ji H: Thrombosis warning in children suffering from henoch-schonlein purpura. Indian J Dermatol. 58:4092013. View Article : Google Scholar : PubMed/NCBI
2	Chen O, Zhu XB, Ren P, Wang YB, Sun RP and Wei DE: Henoch Schonlein Purpura in children: clinical analysis of 120 cases. Afr Health Sci. 13:94–99. 2013.PubMed/NCBI
3	Zaid M, Tan K, Smitasin N, Tambyah PA and Archuleta S: Henoch-Schönlein purpura associated with adult human immunodeficiency virus infection: case report and review of the literature. Ann Acad Med Singapore. 42:358–360. 2013.PubMed/NCBI
4	Wang HL, Liu HT, Chen Q, Gao Y and Yu KJ: Henoch-Schonlein purpura with intestinal perforation and cerebral hemorrhage: a case report. World J Gastroenterol. 19:2574–2577. 2013. View Article : Google Scholar : PubMed/NCBI
5	Ghosh K, Chatterjee A, Sau JT and Dey S: Stroke and skin rash: A rare case of Henoch-Schonlein purpura. Ann Indian Acad Neurol. 15:307–309. 2012. View Article : Google Scholar
6	Fukushima K: Severe intestinal lesions and neuropathy associated with Henoch-Schonlein purpura. Intern Med. 52:2009–2010. 2013. View Article : Google Scholar : PubMed/NCBI
7	Ren X, Zhang W, Dang W, et al: A case of anaphylactoid purpura nephritis accompanied by pulmonary hemorrhage and review of the literature. Exp Ther Med. 5:1385–1388. 2013.PubMed/NCBI
8	Kawasaki Y, Ono A, Ohara S, et al: Henoch-Schonlein purpura nephritis in childhood: pathogenesis, prognostic factors and treatment. Fukushima J Med Sci. 59:15–26. 2013. View Article : Google Scholar
9	An J, Lu Q, Zhao H, Cao Y, Yan B and Ma Z: A study on the association between C1GALT1 polymorphisms and the risk of Henoch-Schonlein purpura in a Chinese population. Rheumatol Int. 33:2539–2542. 2013. View Article : Google Scholar : PubMed/NCBI
10	Wang JJ, Shi YP, Huang Y, Wu C and Li XC: Association of tumor necrosis factor-alpha gene polymorphisms with Henoch-Schonlein purpura nephritis in children. Zhongguo Dang Dai Er Ke Za Zhi. 15:88–90. 2013.(In Chinese). PubMed/NCBI
11	Wang JJ, Shi YP, Yue H, Chun W and Zou LP: CTLA-4 exon 1 +49A/G polymorphism is associated with renal involvement in pediatric Henoch-Schönlein purpura. Pediatr Nephrol. 27:2059–2064. 2012. View Article : Google Scholar : PubMed/NCBI
12	Tabel Y, Mir S and Berdeli A: Interleukin 8 gene 2767 A/G polymorphism is associated with increased risk of nephritis in children with Henoch-Schönlein purpura. Rheumatol Int. 32:941–947. 2012. View Article : Google Scholar
13	Ren SM, Yang GL, Liu CZ, et al: Association between HLA-A and -B polymorphisms and susceptibility to Henoch-Schönlein purpura in Han and Mongolian children from Inner Mongolia. Genet Mol Res. 11:221–228. 2012. View Article : Google Scholar : PubMed/NCBI
14	He X, Lu H, Kang S, et al: MEFV E148Q polymorphism is associated with Henoch-Schönlein purpura in Chinese children. Pediatr Nephrol. 25:2077–2082. 2010. View Article : Google Scholar : PubMed/NCBI
15	Li J and Liu H: P-selectin gene -825 polymorphism is associated with risk of Henoch-Schonlein purpura nephritis. Clin Exp Rheumatol. 29:S1342011.PubMed/NCBI
16	Soylu A, Kizildağ S, Kavukçu S, et al: TLR-2 Arg753Gln, TLR-4 Asp299Gly, and TLR-4 Thr399Ile polymorphisms in Henoch Schonlein purpura with and without renal involvement. Rheumatol Int. 30:667–670. 2010. View Article : Google Scholar
17	Nalbantoglu S, Tabel Y, Mir S and Berdeli A: Lack of association between macrophage migration inhibitory factor gene promoter (−173 G/C) polymorphism and childhood Henoch-Schönlein purpura in Turkish patients. Cytokine. 62:160–164. 2013. View Article : Google Scholar : PubMed/NCBI
18	He X, Li Y, Kang S, et al: The CD18 AvaII polymorphic site not associated with Henoch-Schönlein purpura. Clin Exp Rheumatol. 29:S117–S120. 2011.PubMed/NCBI
19	Torres O, Palomino-Morales R, Miranda-Filloy JA, Vazquez-Rodriguez TR, Martin J and Gonzalez-Gay MA: Lack of association between toll-like receptor 4 gene polymorphism and Henoch-Schönlein purpura. Clin Exp Rheumatol. 28:1102010.
20	López-Mejías R, Sevilla Pérez B, Genre F, et al: No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and Henoch-Schönlein purpura. Tissue Antigens. 82:416–419. 2013. View Article : Google Scholar
21	Torban E, Eccles MR, Favor J and Goodyer PR: PAX2 suppresses apoptosis in renal collecting duct cells. Am J Pathol. 157:833–842. 2000. View Article : Google Scholar : PubMed/NCBI
22	Gelb A, Manligas G, Gharaybeh S and Schimmenti L: Identification of two novel polymorphisms (g.903C>T and g.1544C>T) in the PAX2 gene. Hum Mutat. 17:1552001. View Article : Google Scholar
23	Harshman LA and Brophy PD: PAX2 in human kidney malformations and disease. Pediatr Nephrol. 27:1265–1275. 2012. View Article : Google Scholar
24	Porteous S, Torban E, Cho NP, et al: Primary renal hypoplasia in humans and mice with PAX2 mutations: evidence of increased apoptosis in fetal kidneys of Pax2(1Neu) +/− mutant mice. Hum Mol Genet. 9:1–11. 2000. View Article : Google Scholar
25	Thomas R, Sanna-Cherchi S, et al: HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatr Nephrol. 6:897–903. 2011. View Article : Google Scholar
26	Zu CP, Yi ZW and Dang XQ: Significance of PAX2 expression in pathological kidney of children with Henoch-Schoenlein purpura nephritis. Journal of Clinical Research. 22:1514–1517. 2005.
27	Yi ZW, Fang XL, Wu XC, et al: Role of PAX2 gene polymorphisms in Henoch-Schonlein purpura nephritis. Nephrology (Carlton). 11:42–48. 2006. View Article : Google Scholar
28	Loghman-Adham M: Evaluating proteinuria in children. Am Fam Physician. 58:1145–1152. 1158–1149. 1998.PubMed/NCBI
29	No authors listed. Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. Kidney Int. 20:765–771. 1981. View Article : Google Scholar : PubMed/NCBI
30	Miller SA, Dykes DD and Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16:12151988. View Article : Google Scholar : PubMed/NCBI
31	Tellier AL, Amiel J, Delezoide AL, et al: Expression of the PAX2 gene in human embryos and exclusion in the CHARGE syndrome. Am J Med Genet. 93:85–88. 2000. View Article : Google Scholar : PubMed/NCBI
32	Schimmenti LA, Cunliffe HE, McNoe LA, et al: Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations. Am J Hum Genet. 60:869–878. 1997.PubMed/NCBI
33	Shim HH, Nakamura BN, Cantor RM and Schimmenti LA: Identification of two single nucleotide polymorphisms in exon 8 of PAX2. Mol Genet Metab. 68:507–510. 1999. View Article : Google Scholar : PubMed/NCBI
34	Ballinger S: Henoch-Schonlein purpura. Curr Opin Rheumatol. 5:591–594. 2003. View Article : Google Scholar