ZASP基因与特发性扩张型心肌病相关性研究

The correlation between zasp gene and idiopathic dilated cardiomyopathy

目的探讨成都地区特发性扩张型心肌病(IDCM)人群中是否存在Z带选择性缝接PDZ基序蛋白(ZASP)基因突变以及与该地区IDCM患者的相关性。方法2006年1月至2007年12月在四川大学华西医院采用聚合酶链反应-单链构象多态性技术(PCR-SSCP)结合DNA测序方法,筛检成都地区无血缘关系汉族人群(包括120例IDCM患者,100名健康对照者)ZASP基因外显子4、6、10的可能突变位点。结果在IDCM组和正常对照组中,ZASP基因外显子4、6单链构象多态性(SSCP)电泳图谱未发现差异;但外显子10SSCP电泳图谱发现差异,经DNA测序证实为G216T杂合子与T216T纯合子。G216T杂合子在IDCM组检出28例,对照组检出12例;T216T纯合子在IDCM组检出9例,对照组检出4例。G/T基因型及T等位基因频率在IDCM组和对照组中差异有统计学意义(P<0.05)。结论ZASP基因外显子10G216-T多态性与成都地区汉族IDCM患者遗传易感性相关;提示T等位基因为扩张型心肌病的易感基因。

Objective To explore the existance of ZASP （ Z-band alternatively spliced PDZ-motif protein） gene mutations in idiopathic dilated cardiomyopathy （IDCM）patients in Chengdu and to study the relationship between this gene and IDCM. Methods Polymerase chain reaction-single-strand conformation polymorphism （SSCP）and DNA sequencing techniques were used to screening the possible mutation site of the ZASP gene exon 4,6,10,in the unrelated Han ethnic population of Chengdu area（ including 120 IDCM patients and 100 normal controls）. Results The difference of SSCP patterns were found on exon 10 of ZASP gene between IDCM and control groups. The DNA direct sequencing analysis of exon 10 revealed heterozygote G216T and homozygote T216T. G216T was only founded in 28 IDCM patients and 12 controls. T216T was only found 9 patients and 4 controls. Compared with controls, IDCM patients had different frequencies of the GT genotype and T allele（P 〈0. 05）. Conclusion The G216-T polymorphism of exon 10 in ZASP gene is related to the susceptibility to IDCM in the Han ethnic population of Chengdu area, indicating that T allelemay may be predisposing gene of IDCM.