Advances in Clinical and Experimental Medicine
2017, vol. 26, nr 4, July, p. 661–664
PubMed ID: 28691415
Publication type: original article
Association of ACE, VEGF and CCL2 gene polymorphisms with Henoch–Schönlein purpura and an evaluation of the possible interaction effects of these loci in HSP patients
1 Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
2 University of Tabriz
3 Liver and Gastrointestinal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Background. Henoch–Schönlein purpura (HSP) is a multisystem, small vessel, leucocytoclastic vasculitis. It is predominantly a childhood vasculitis, rarely reported in adults. Studies have shown that several different genetic factors such as genes involved in inflammatory system and renin-angiotensin system (RAS) are important in the pathogenesis of Henoch–Schönlein purpura.
Objectives. The purpose of this study was to evaluate the independent effect of 3 gene polymorphisms including CCL2-2518 C/T, VEGF-634G/C and ACE(I/D) with HSP disease and their possible joint interactions in developing the disease.
Material and Methods. In this case-control study 47 HSP cases and 74 unrelated healthy controls were enrolled for evaluation. All individuals were genotyped for CCL2-2518C/T, VEGF-634G/C and ACE(I/D) gene polymorphisms. The possible association of these polymorphisms with susceptibility to develop HSP disease independently and in different joint combinations was evaluated.
Results. The frequencies of TT genotype and T allele of CCL2-2518C/T gene polymorphism and CC genotype and C allele of VEGF-634G/C gene polymorphism were significantly high in HSP children (p-values = 0.005 and = 0.007 respectively). Interestingly, studying the joint interaction of these 2 genotypes (CC genotype of VEGF G-634C and TT genotype of CCL2 C-2518T) in this cohort showed a more significant effect in the development of the disease (p < 0.000, OR = 6.009). The frequency of TT genotype of CCL2 gene when combined with II genotype of ACE gene in HSP children was significantly higher (p < 0.000, OR = 4.213).
Conclusion. The results of this pilot study provide evidence of the possible gene–gene interaction effects of CCL2, VEGF and ACE genes in developing HSP disease.
CCL2, VEGF, Henoch–Schönlein purpura, gene–gene interaction effect, ACE
- Kamath N, Rao S. Henoch–Schönlein purpura: An update. Indian J Rheumatol. 2012;7:92–98.
- Jithpratuck W, Elshenawy Y, Saleh H, Youngberg G, Chi D, Krishnaswamy G. The clinical implications of adult-onset Henoch-Schönelin purpura. Clin Mol Allergy. 2011;7:92–98.
- Rigante D, Castellazzi L, Bosco A, Esposito S. Is there a crossroad between infections, genetics, and Henoch–Schönlein purpura? Autoimmun Rev. 2013;12:1016–1021.
- Yang YH, Lai HJ, Kao ChK, Lin YT, Chiang BL. The association between transforming growth factor-b gene promoter C-509T polymorphism and Chinese children with Henoch-Schönlein purpura. Pediatr Nephrol. 2004;19:972–975.
- Topaloglu R, Sungur A, Baskin E, Besbas N, Saatci U, Bakkaloglu A. Vascular endothelial growth factor in Henoche-Schönlein purpura. J Rheumatol. 2001;28:2269e73.
- Yang YH, Huang MT, Lin SC, Lin YT, Tsai MJ, Chiang BL. Increased transforming growth factor-beta (TGF-beta)-secreting T cells and IgA anti-cardiolipin antibody levels during acute stage of childhood Henoche-Schönlein purpura. Clin Exp Immunol. 2000;122: 285–290.
- Yang YH , Huang YH , Lin YL, et al. Circulating IgA from acute stage of childhood HenocheSchonlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway. Clin Exp Immunol. 2006;144:247e53.
- Pavkova Goldbergovaa M, Lipkovaa J, Paveka N, et al. RANTES, MCP-1 chemokines and factors describing rheumatoid arthritis. Molecular Immunology 2012;52:273–278.
- Yu HH, Liu PH, Yang YH, et al. Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoche Scho¨nlein purpura susceptibility and severity. Journal of the Formosan Medical Association published on 21 December 2012.doi:10.1016/ j.jfma.2012.12.007
- Zeng HS, Xiong XY, Chen YY, Luo XP. Gene polymorphism of vascular endothelial growth factor in children with Henoche-Schönlein purpura nephritis. Chinese Journal Of Contemporary Pediatrics. 2009;11:417–421.
- Nalbantoglua S, Tabelb Y, Mirc S, Serdaroglud E , Berdelia A. Association between RAS gene polymorphisms (ACE I/D, AGT M235T) and Henoche-Schönlein purpura in a Turkish population. Dis Markers. 2013;34:23–32.
- Dudley J, Afifi E, Gardner A, Tizard EJ, McGraw ME. Polymorphism of the ACE gene in Henoch-Schönlein purpura nephritis. Pediatr Nephrol. 2000;14:218–220.
- Yoshioka T, Xu YX, Yoshida H, Shiraga H, Muraki T, Ito K. Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schönlein purpura nephritis. Arch Dis Child. 1998;79:394–399
- Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res. 1988;16:1215.
- Prior SJ, Hagberg JM, Paton CM, et al. DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygene consumption. Am J Physiol Heart Cric Phisiol. 2006;5:848–855.
- Bonyadi M, Mohammadian T, Rafeey M, et al. Chemokine MCP1/CCL2 gene polymorphism influences Henoche-Schönlein purpura susceptibility in Iranian Azeri–Turkish patients. 2015;54:1269–1274.
- Bonnet F, Patel S, Laville M, et al. Influence of the ACE gene insertion/deletion polymorphism on insulin sensivity and impaired glucose tolerance in healthy subjects. Diabete Care. 2008;4:789–794.
- Cekmen M, Evereklioglu C, Er H, et al. Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behçet’s syndrome. Int J Dermatol. 2003;42:870–875.
- Rueda B, Perez-Armengol C, Lopez-Lopez S, Garcia-Porrua C, Martin J, Gonzalez-Gay MA. Association between functional haplotypes of vascular endothelial growth factor and renal complications in HenocheSchonlein purpura. J Rheumatol. 2006;33:69e73.
- Amoroso A, Danek G, Vatta S, et al. Polymorphism angiotensin converting enzyme and severety of renal disease in Henoche-Schönlein patient Nephrol. Dial Transplant. 1998;13:3184–3188.
- Liu D, Lu F, Zhai S, et al. Renin-angiotensin system gene polymorphisms in children with Henoche-Schönlein purpura in West China. J Renin Angiotensin Aldosterone Syst. 2010;11:248–255.