Abstract OBJECTIVE: To study the relationship of -634G/C gene polymorphism of vascular endothelial growth factor (VEGF) with Henoch-Schonlein purpura nephritis (HSPN) in children. METHODS: One hundred ethnic Han children with HSP, including 50 children with concurrent nephritis (HSPN group) and 50 children without nephritis (HSP without nephritis group), were enrolled. Fifty age-, sex-and ethnics-matched healthy children were used as the control group. VEGF-634G/C genotypes were determined by PCR-RFLP. Plasma VEGF levels were measured using ELISA. RESULTS: CC genotype distribution (32%) and C allele frequency (56%) in the HSPN group were significantly higher than those in the control group (10% and 35% respectively) and the HSP without nephritis group (10% and 33% respectively) (P<0.01). The incidence of nephritis in HSP patients with CC genotype increased significantly when compared with those with GG genotype (76% vs 31%; P<0.01). Plasma VEGF levels in patients with CC genotype (180.5±40.7 pg/mL) were significantly higher than those in patients with CG (145.2±48.3 pg/mL) and GG (101.5±26.5 pg/mL) genotypes (P<0.05). CONCLUSIONS: VEGF-634G/C gene polymorphism may be associated with the development of HSPN. C allele may a susceptible gene of HSPN.[Chin J Contemp Pediatr, 2009, 11 (6):417-421]
ZENG Hua-Song,XIONG Xiao-Yan,CHEN Yao-Yong et al. Gene polymorphism of vascular endothelial growth factor in children with Henoch-Schonlein purpura nephritis[J]. 中国当代儿科杂志, 2009, 11(06): 417-421.
ZENG Hua-Song,XIONG Xiao-Yan,CHEN Yao-Yong et al. Gene polymorphism of vascular endothelial growth factor in children with Henoch-Schonlein purpura nephritis[J]. CJCP, 2009, 11(06): 417-421.
[1]Topaloglu R, Sungur A, Baskin E, Besbas N, Saatci U, Bakkaloglu A. Vascular endothelial growth factor in Henoch-Schonlein purpura[J]. J Rheumatol, 2001, 28(10):2269-2273.
[2]Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production[J]. Cytokine, 2000, 12(8):1232-1235.
[3]Awata T, Inoue K, Kurihara S, Ohkubo T, Watanabe M, Inukai K, et al. A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes[J]. Diabetes, 2002,51(5):1635-1639.
[4]Abe A, Sato K, Habuchi T, Wang L, Li Z, Tsuchiya N, et al. Single nucleotide polymorphisms in the 3′untranslated region of vascular endothelial growth factor gene in Japanese population with or without renal cell carcinoma[J]. Tohoku J Exp Med, 2002,198(3):181-190.
[5]Shahbazi M, Fryer AA, Pravica V, Brogan IJ, Ramsay HM, Hutchinson IV, et al. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection[J]. J Am Soc Nephrol, 2002,13(1):260-264.
[6]McCarron SL, Edwards S, Evans PR, Gibbs R, Dearnaley DP, Dowe A, et al. Influence of cytokine gene polymorphisms on the development of prostate cancer[J]. Cancer Res, 2002,62(12):3369-3372.
[7]Howell WM, Bateman AC, Turner SJ, Collins A, Theaker JM. Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma[J]. Genes Immun, 2002, 3(4):229-232.
[8]Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E. A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels[J]. J Vasc Res, 2000, 37(6):443-448.
[9]Brogan IJ, Khan N, Isaac K, Hutchinson JA, Pravica V, Hutchinson IV. Novel polymorphisms in the promoter and 5′ UTR regions of the human vascular endothelial growth factor gene[J]. Hum Immunol, 1999, 60(12):1245-1249.
[10]Rueda B, Perez-Armengol C, Lopez-Lopez S, Garcia-Porrua C, Martín J, Gonzalez-Gay MA. Association between functional haplotypes of vascular endothelial growth factor and renal complications in Henoch-Schonlein purpura[J]. J Rheumatol, 2006, 33(1):69-73.
[11]Habib R, Niaudet R, Levy M. Schoenlein-Henoch purpura nephritis and IgA nephropathy[M].//Tisher CC, Brenner BM. Renal Pathology with Clinical and Functional Correlations. 2nd ed. Philadelphia: Lippincott, 1994, 427-523.
[12]Haycock GB. The nephritis of Henoch-Schoenlein purpura[M].//Cameron JS. Oxford Textbook of Nephrology. 2nd ed. Oxford: Oxford University Press, 1998, 585-612.
[13]Niaudet P, Habib R. Methylprednisolone pulse therapy in the treatment of severe forms of Schoenlein-Henoch purpura nephritis[J]. Pediatr Nephrol, 1998, 12(3):238-243.
[14]Watanabe T, Takahashi S, Nakajo S, Hamasaki M. Pathological improvement of IgA nephropathy and Henoch-Schoenlein purpura nephritis with urokinase therapy[J]. Acta Paediatr Japonica, 1996, 38(6):622-628.
[15]Coppo R, Mazzucco G, Cagnoli L, Lupo A, Schena FP. Long-term prognosis of Henoch-Schonlein nephritis in adults and children. Italian Group of Renal Immunopathology Collaborative Study on Henoch-Schonlein purpura[J]. Nephrol Dial Transplant, 1997, 12(1):2277-2283.
[16]Counahan R, Winterborn MH, White RH, Heaton JM, Meadow SR, Bluett NH, et al. Prognosis of Henoch-Schonlein nephritis in children[J]. Br Med J, 1977, 2(6078):11-14.
[17]Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins[J]. Endocr Rev, 1992, 13(1):18-32.
[18]Vincenti V, Cassano C, Rocchi M, Persico G. Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3[J]. Circulation, 1996, 93(8):1493-1495.
[19]Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor[J]. Endocr Rev, 1997, 18(1):4-25.
[20]Rahimi N, Dayanir V, Lashkari K. Receptor chimeras indicate that the vascular endothelial growth factor receptor-1 (VEGFR-1) modulates mitogenic activity of VEGFR-2 in endothelial cells[J]. J Biol Chem, 2000, 275(22):16986-16992.
[21]Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marmé D. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1[J]. Blood, 1996, 87(8):3336-3343.
[22]Clauss M, Weich H, Breier G, Knies U, Rockl W, Waltenberger J, et al. The vascular endothelial growth factor receptor Flt-1 mediates biological activities: implications for a functional role of placenta growth factor in monocyte activation and chemotaxis[J]. J Biol Chem, 1996, 271(30):17629-17634.
[23]Awata T, Kurihara S, Takata N, Neda T, Iizuka H, Ohkubo T, et al. Functional VEGF C-634G polymorphism is associated with development of diabetic macular edema and correlated with macular retinal thickness in type 2 diabetes[J]. Biochem Biophys Res Commun, 2005, 333(3): 679-685.
[24]Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F, Marklund SL, et al. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death[J]. Nat Genet, 2003, 34(4): 383-394.
[25]Bornes S, Boulard M, Hieblot C, Zanibellato C, Iacovoni JS, Prats H, et al. Control of the vascular endothelial growth factor internal ribosome entry site (IRES) activity and translation initiation by alternatively spliced coding sequences[J]. J Biol Chem, 2004, 279(18):18717-18726.
[26]Huez I, Bornes S, Bresson D, Creancier L, Prats H. New vascular endothelial growth factor isoform generated by internal ribosome entry sitedriven CUG translation initiation[J].Mol Endocrinol, 2001,15(12):2197-2210.
[27]Lambrechts D, Devriendt K, Driscoll DA, Goldmuntz E, Gewillig M, Vlietinck R, et al. Low expression VEGF haplotype increases the risk for tetralogy of Fallot: a family based association study[J]. J Med Genet, 2005, 42(6):519-522.