Abstract：Objective To examine the single nucleotide polymorphism (SNP) (rs1495592) in transforming growth factor-beta receptor 2 (TGFBR2) gene in children, and to investigate its association with Kawasaki disease (KD) and coronary artery lesions (CALs). Methods Thirty-five KD patients, 14 of whom had CALs (CAL subgroup), were selected as the case group, and 25 healthy age-matched children were selected as the control group. The SNP (rs1495592) in TGFBR2 gene was studied by gene sequencing. The association of SNP (rs1495592) with KD and (CALs) was analyzed based on the sequencing results. Results There were no significant differences in genotype frequency distribution (χ2=0.566, P=0.452) and allele frequency distribution (χ2=0.216, P=0.642) between the two groups. Genotypes in the CAL subgroup included CC (21.4%) and CT+TT (78.6%), while genotypes in the non-CAL subgroup included CC (61.9%) and CT+TT (38.1%). There was significant difference in genotype frequency distribution between the two groups (χ2=5.546, P=0.019), but without significant difference in allele frequency distribution (χ2=3.673, P=0.055). Conclusions The SNP (rs1495592) in TGFBR2 gene may not be associated with development of KD in children, but it is associated with CALs in children with KD.
SHI Cui-Ping,ZHANG Hong-Yan. Association of single nucleotide polymorphism in TGFBR2 gene with Kawasaki disease and coronary artery lesions[J]. CJCP, 2013, 15(9): 767-770.
Ruiz-Ortega M, Rodriguez-Vita J, Sanchez-Lopez E, Carvajal G, Egido J. TGF-beta signaling in vascular fibrosis[J]. Cardiovasc Res, 2007, 74(2): 196-206.
[4]
Clark-Greuel JN, Connolly JM, Sorichillo E, Narula NR, Rapoport HS, Mohler ER 3rd, et al. Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events[J]. Ann Thorac Surg, 2007, 83(3): 946-953.
[5]
Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling[J]. Nature, 2003, 425(6958): 577-584.
[6]
Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus[J]. Cell, 2003, 113(6): 685-700.
[7]
Wu Y, Li Q, Zhou X, Yu J, Mu Y, Munker S, et al. Decreased Levels of Active SMAD2 Correlate with Poor Prognosis in Gastric Cancer[J]. PLoS One, 2012, 7(4): e35684.
Choi YM, Shim KS, Yoon KL, Han MY, Cha SH, Kim SK,et al. Transforming growth factor beta receptor II polymorphisms are associated with Kawasaki disease[J]. Korean J Pediatr, 2012, 55(1): 18-23.
Shimizu C, Jain S, Davila S, Hibberd ML, Lin KO, Molkara D, et al. Transforming growth factor-beta signaling pathway in patients with Kawasaki disease[J]. Circ Cardiovasc Genet, 2011, 4(1): 16-25.
[16]
Gilbert RS, Kobayashi R, Sekine S, Fujihashi K. Functional Transforming Growth Factor-β Receptor Type II Expression by CD4+ T Cells in Peyer's Patches Is Essential for Oral Tolerance Induction[J]. PLoS One, 2011, 6(11): e27501.
[17]
Sohn SY, Song YW, Yeo YK, Kim YK, Jang GY, Woo CW, et al. Alteration of CD4+ CD25+ Foxp3 T cell level in kawasaki disease[J]. Korean J Pediatr, 2011, 54(4): 157-162.
Park SO, Lee YJ, Seki T, Hong KH, Fliess N, Jiang Z, et al. ALK5-and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2[J]. Blood, 2008, 111(2): 633-642.
[22]
Baas AF, Medic J, van't Slot R, de Kovel CG, Zhernakova A, Geelkerken RH, et al. Association of the TGF-beta receptor genes with abdominal aortic aneurysm[J]. Eur J Hum Genet, 2010, 18(2): 240-244.
