基质金属蛋白酶-9基因-1562C/T多态性与川崎病冠脉损害及丙种球蛋白耐药的关系

Relationship of Matrix Metalloproteinase-9(MMP-9) gene-1562 C/T Polymorphism,Coronary Artery Lesions(CAL) and Intravenous Immunoglobulin Treatment(IVIG) Resistance in Children with Kawasaki Disease

目的研究基质金属蛋白酶-9(MMP-9)基因启动子区-1562 C/T多态性与川崎病(KD)冠状动脉损害(CAL)及与丙种球蛋白(IVIG)耐药的关系。方法收集2010年3月～2012年2月期间确诊KD的住院患儿资料,共124例,其中男性78例,女性46例,平均年龄25.8个月(4个月～67个月)。根据病程中心脏彩超检查的冠脉情况,将124例患儿分为CAL组(21例)和无CAL组(103例)。根据患儿对IVIG的反应,将124例患儿分为IVIG耐药组(14例)和IVIG敏感组(110例)。检测并分析所有KD患儿的MMP-9-1562 C/T基因型频率及等位基因频率,研究其与CAL及IVIG耐药的关系。结果 CAL组中CC/CT基因型频率CC为66.7%,CT为33.3%,与无CAL组(CC为88.3%,CT为11.7%)比较差异有统计学意义(χ2=6.321,P=0.020)。CAL组C/T等位基因频率为C为83.3%,T为16.7%,与无CAL组(C为94.2%,T为5.8%)比较差异有统计学意义(χ2=5.796,P=0.025),并且Logistic回归分析示1562T等位基因是KD患儿发生CAL的危险因素(χ2=5.756,P=0.016,OR=3.792)。IVIG耐药组与IVIG敏感组中MMP-9-1562 CC/CT基因型频率及C/T等位基因频率均无显著统计学意义。结论MMP-9基因-1562C/T多态性与CAL有关,-1562T等位基因加大了KD患儿发生CAL的风险。-1562T等位基因与KD患儿IVIG耐药无明显关系。

Objective To investigate the relationship of matrix metalloproteinase - 9 （ MMP - 9 ） gene - 1562 C/T polymorphism, coronary artery lesions （CAL） and intravenous immunoglobulin treatment （IVIG） resistance in children with Kawasaki disease （KD）. Methods Totally 124 pediatric cases of KD （78 boys and 46 girls）, the average age was 25.8 months （4 - 67 months）. These cases ac- cording to the echocardiography results were divided into CAL group （21 cases） and non -CAL group （103 cases） ; secondary according to their responses to IVIG into resistance group （14 cases） and IVIG responsive group （110 cases）. Promoter 1562 C/T gene polymor- phism of MMP-9 were tested in all of these cases. The relationship of MMP-9 gene- 1562 C/T polymorphism, CAL and IVIG resist- ance were analyzed. Results The results of genetic polymorphism analysis showed that the frequency of CT genotype （33.3%） in CAL group was significantly higher than that （ 11.7% ） in non - CAL group （X2 = 6. 321 ,P = 0. 020）. The frequency of T allele （ 16.7% ） in CAL group was significantly higher than that （5.8%） in non - CAL group （X2 = 5. 796 ,P = 0. 025 ）. The cases carrying the - 1562T al- lele were even more easily developing into CAL （X2 = 5. 756 ,P = 0. 016, OR = 3. 792 ）. The frequency of CC/CT genotype or C/T allele showed no significant difference between IVIG resistance group and IVIG responsive group. Conclusion The genetic polymorphism in MMP - 9 gene - 1562C/T is associated to CAL in children with KD. The T allele is a risk factor of CAL. Due to the frequency of CC/CT showed above there is no significant association between T allele and IV1G resistance in KD.