单核细胞趋化因子-1基因多态性与川崎病的相关性研究

Association between polymorphisms of monocyte chemoattractant protein 1 gene and Kawasaki disease

目的探讨川崎病(KD)患儿单核细胞趋化因子-1(MCP-1)基因-2518G/A多态性与KD易感性及并发冠状动脉损伤(CAL)之间的关系。方法收集2004年9月至2006年5月在西安市儿童医院确诊为KD的住院患儿共62例。MCP-1基因-2518G/A多态性检测采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,62例中无冠脉病变组(NCAL组)39例,合并冠脉病变组(CAL组)23例。随机选择正常健康儿童60名作为正常对照组。同时采用双抗体夹心酶联免疫吸附法(ELISA)检测所有KD患儿及健康儿童血清MCP-1水平。结果在健康儿童中,MCP-1-2518G等位基因频率(53.3%)分别与高加索人群(29%)、非洲人群(22%)相比明显增加;与韩国人(65%)、墨西哥人(47%)比较,差异无统计学意义。陕西地区健康儿童与KD患儿MCP-1-2518G/A等位基因频率组间比较差异无统计学意义;KD组内G/G基因型MCP-1浓度较G/A基因型和A/A基因型MCP-1浓度增高,差异有统计学意义(P<0.01);CAL组MCP-1浓度较NCAL组增高;CAL组G/G基因型、G/A基因型MCP-1浓度与NCAL组比较均明显增高,差异有统计学意义(P<0.05)。结论陕西省儿童与不同种族人群MCP-1-2518G/A等位基因存在多态性差异,而该基因多态性对KD发生的易感性可能不产生影响,但在一定程度上可能对KD伴发CAL产生重要影响。

Objective To investigate the polymorphisms of monocyte chemoattractant protein 1 （MCP-1 ） gene in chil- dren with Kawasaki disease （KD） in Shannxi province and association between the polymorphisms and coronary artery lesion （CAL） in KD. Methods A total of 2 in-patients who were diagnosed with KD wei＇e divided into two groups： 39 cases with CAL group （CAL group） and 23 cases without CAL group（NCAL group） ; in addition, 60 healthy children were randomly regarded as control group, respectively. The-2518 codon genotype of MCP-1 gene were screened with polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP） , and the serum concentration of MCP-1 were detected by enzyme linked immunosorbent assay （ELISA） for all of them. Results 1. The allele frequen- cy of the MCP-1 gene regulatory region -2518 G was significantly higher in heathy children of Shannxi region（53.3%） than in Caucasian and African （29% vs 22%）, while it had no statistic significance compared with Korean and Mexican （65% vs 47% ）. 2. The allele frequency of MCP-1 gene mutation had significant difference between KD patients and heathy children in Shannxi region. 3. The serum MCP-1 concentration of patients with G/G genotype was remarkably in- creased compared with that of patients with G/A or MA genotype in KD group （P 〈 0.01 ）. 4. The level of MCP-1 was significantly higher in CAL group than in NCAL group. Compared with the serum MCP-1 concentration of patients with G/G or G/A genotype in NCAL group, there was significant increase in CAL group （P 〈 0.05）. Conclusion There is polymorphic difference of allele frequency of-2518 co- don G/A mutation of MCP-1 gene between children in Shannxi region and different ethnic populations, while polymorphisms of the gene may not contribute to sensitivity for KD. Nevertheless, the polymorphic deviation may influence KD accompanied by CAL to some extent.