Abstract：OBJECTIVE: To study the association of FCGR2A gene single nucleotide polymorphism (SNP) rs1801274 with Kawasaki disease (KD) susceptibility and the efficacy of intravenous immunoglobulin (IVIG) therapy in Han Chinese children. METHODS: Thirty-five KD children and 25 age-and gender-matched healthy children (control group) were enrolled in the study. Polymerase chain reaction (PCR) and gene sequence analysis were applied to detect SNP of FCGR2A gene rs1801274. These KD patients were classified into two subgroups based on the presence of coronary artery lesion (CAL) following IVIG therapy: CAL (n=13) and non-CAL (n=22). RESULTS: FCGR2A gene SNP rs1801274 was detected in all subjects, including three genotypes (AA, AG and GG). For FCGR2A gene SNP rs1801274, there were significant differences in the genotype and allele frequencies between the KD and control groups (P<0.05), and significant differences in the genotype and allele frequencies were also found between the CAL and non-CAL subgroups (P<0.05). A allele and AA genotype were linked to an increased risk of KD susceptibility (A allele: OR=3.39, 95%CI:1.53-7.50; AA genotype: (OR=4.93, 95%CI:1.61-15.1). Both AG (OR=5.43, 95%CI:1.06-27.8) and G allele (OR=4.88, 95%CI:1.44-16.5) were linked to an increased risk of CAL in KD children. CONCLUSIONS: Polymorphism of the FCGR2A gene SNP rs1801274 is one of the important factors probably influencing susceptibility to KD and efficacy of IVIG therapy on KD in Han Chinese children.
JI Yu-Xiao,ZHANG Hong-Yan,LIN Shu-Xiang. Single nucleotide polymorphism of FCGR2A gene in Han Chinese children with Kawasaki disease[J]. CJCP, 2013, 15(3): 196-200.
［1］Wallace CA, French JW, Kahn SJ, Sherry DD. Initial intravenous gammaglobulin treatment failure in Kawasaki disease［J］.Pediatrics, 2000, 105（6）: E78.
［2］Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin［J］.N Engl Med, 2001, 345(10): 747-755.
［4］Abe J, Jibiki T, Noma S, Nakajima T, Saito H, Terai M. Gene expression profiling of the effect of high-dose intravenous Ig in patients with Kawasaki disease［J］. J Immunol, 2005, 174(9): 5837-5845.
［5］Taniuchi S, Masuda M, Teraguchi M, Ikemoto Y, Komiyama Y, Takahashi H, et al. Polymorphism of fcgamma riia may affect the efficacy of gamma-globulin therapy in Kawasaki disease［J］. Clin Immunol, 2005, 25(4): 309-313.
［6］Biezeveld M, Geissler J, Merkus M, Kuipers IM, Ottenkamp J, Kuijpers T. The involvement of fc gamma receptor gene polymorphisms in kawasaki disease［J］. Clin Exp Immunol, 2006, 147(1): 106-111.
［7］Khor CC, Davila S, Breunis WB, Lee YC, Shimizu C, Wright VJ, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease［J］.Nat Genet, 2011, 43(12): 1241-1246.
［8］Lee YC, Kuo HC, Chang JS, Chang LY, Huang LM, Chen MR, et al. Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis［J］. Nat Genet, 2012, 44(5): 522-525
［9］Onouchi Y, Ozaki K, Burns JC, Shimizu C, Terai M, Hamada H, et al. A genome-wide association study identifies three new risk loci for Kawasaki disease［J］. Nat Genet, 2012, 44(5): 517-521.
［10］Shrestha S, Wiener H, Shendre A, Kaslow RA, Wu J, Olson A, et al.Role of activating FcγR gene polymorphisms in Kawasaki disease susceptibility and intravenous immunoglobulin response［J］. Circ Cardiovasc Genet, 2012, 5(3): 309-316.
［11］Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. Diagnosis,treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease,Council on Cardiovascular Disease in the Young. American Heart Association［J］. Pediatrics, 2004, 114(6): 1708-1733.
［12］Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition)［J］. Pediatr Int, 2005, 47(2): 232-234.
［13］van de Winkel JG, Anderson CL. Biology of human immunoglobulin G Fc receptors［J］. Leukoc Biol, 1991, 49(5): 511-524.
［14］Sinha S, Prasad KN, Jain D, Nyati KK, Pradhan S, Agrawal S. Immunoglobulin IgG Fc-receptor polymorphisms and HLA class II molecules in Guillain-Barré syndrome［J］. Acta Neurol Scand, 2010, 122(1): 21-26.
［15］Meziani R, Yamada R, Takahashi M, Ohigashi K, Morinobu A, Terao C, et al. A trans-ethnic genetic study of rheumatoid arthritis identified FCGR2A as a candidate common risk factor in Japanese and European populations［J］. Mod Rheumatol, 2012, 22(1): 52-58.
［16］Yang SK, Jung Y, Kim H, Hong M, Ye BD, Song K. Association of FCGR2A,JAK2 or HNF4A variants with ulcerative colitis in Koreans［J］. Dig Liver Dis, 2011, 43(11): 856-861.
［17］Gordon JB, Kahn AM, Burns JC. When children with Kawasaki disease grow up: Myocardial and vascular complications in adulthood［J］. Am Coll Cardiol, 2009, 54(21): 1911-1920.
［18］Tsujimoto H, Takeshita S, Nakatani K, Kawamura Y, Tokutomi T, Sekine I. Intravenous immunoglobulin therapy induces neutrophil apoptosis in Kawasaki disease［J］. Clin Immunol, 2002, 103(2): 161-168.
［19］Hui-Yuen JS, Duong TT, Yeung RS.TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease［J］. J Immunol, 2006, 176(10): 6294-6301.
［20］Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, et al. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease［J］. J Pediatr, 2008, 153(6): 833-838.
［21］Son MB, Gauvreau K, Burns JC, Corinaldesi E, Tremoulet AH, Watson VE, et al. Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study［J］. J Pediatr, 2011, 158(4): 644-649.
［22］Onouchi Y. Molecular genetics of Kawasaki disease［J］. Pediatr Res, 2009, 65(5 Pt 2): 46R-54R.
