CASP3基因一个新的功能性SNP rs72689236与川崎病相关性的Meta分析

Association of new functional SNP rs72689236 of CASP3 with Kawasaki disease: a meta-analysis

目的综合分析半胱氨酸蛋白酶3基因(CASP3)一个新的功能性单核苷酸多态位点(SNP)rs72689236与川崎病发生发展的相关性。方法国内外数据库中检索川崎病与CASP3基因相关性研究的文献,根据纳入与排除标准筛选文献,获取2012年11月以前公开发表的病例-对照研究与家系传递不平衡研究(TDT)的资料,结合作者的相关研究结果,评价质量后采用RevMan 5.1软件进行Meta分析。结果川崎病患者中rs72689236的A等位基因频率显著增高(P<0.001,OR=1.34,95%CI:1.24～1.46)。rs72689236风险等位基因A的携带者(AG+AA)相较于GG个体,患病风险增加约44%(P<0.001,OR=1.44,95%CI:1.27～1.65)。该SNP的风险等位基因A增加了川崎病并发冠状动脉损伤的风险(P=0.01,OR=1.51,95%CI:1.10～2.07),携带风险等位基因A的川崎病患者相比于非携带者,并发冠状动脉损伤的风险增加约59%(P=0.05,OR=1.59,95%CI:1.00～2.53)。未发现该SNP与川崎病患者静脉注射免疫球蛋白(IVIG)疗效相关联的证据。结论 CASP3基因功能性SNP rs72689236的A等位基因增加了川崎病的发生风险,该SNP的风险等位基因有可能作为川崎病并发冠状动脉损伤的易感遗传标记。目前还没有足够的证据提示该SNP对川崎病的重要治疗手段IVIG的疗效存在影响,需要更多的相关研究以进一步评价其应用于临床个体化治疗方案选择的可行性。

Objective To investigate the association of rs72689236, a new functional single nucleotide polymorphism （SNP） of the gene encoding caspase-3 （ CASF＇3 ）, with the occurrence and development of Kawasaki disease by a meta analysis. Methods A literature search was performed using databases at home and abroad according to inclusion and exclusion criteria, to acquire studies on the relationship between rs72689236 and Kawasaki disease published up to November 2012, including case-control studies and transmission disequilibrium tests. An integrated meta analysis was performed using RevMan 5.1 software after the studies were screened and evaluated. Results Six studies were extracted for systematic review of the association between rs72689236 and Kawasaki disease. The frequency of allele A of the SNP was significantly higher in patients with Kawasaki disease than in the controls （ OR = 1.34, 95% CI = 1.24 - 1.46, P 〈0. 001 ） ; the risk for Kawasaki disease in children with allele A （AA ＋ AG ） increased by approximately 44% compared with children with GG （ OR = 1.44, 95% C1 = 1.27 - 1.65, P 〈 0.00l ）. The frequency of allele A of the SNP was significantly higher in Kawasaki disease patients with coronary artery lesions than in those without coronary artery lesions （ OR = 1.51, 95% CI = 1.10-2. 07, P = 0. O1 ） ; the risk for coronary artery lesions in Kawasaki disease patients with allele A （AA ＋ AG） increased by approximately 59% compared with Kawasaki disease patients with GG （ OR = 1.59, 95% CI = 1. O0 - 2. 53, P = O. 05 ]. No association between this SNP and the therapeutic effect of intravenous immunoglobulin （IVIG） was found in patients with Kawasaki disease. Conclusions The allele A of functional SNP rs72689236 of CASP3 increases the risk for Kawasaki disease, and it may be used as the genetic marker for susceptibility to coronary artery lesions as a complication of Kawasaki disease. Currently, there is still no sufficient evidence that this SNP has an impact on the therapeutic effect of IVIG in patients with Kawasaki disease, and more studies are needed to investigate the feasibility of its application in individualized treatment.