摘要
基因的单核苷酸多态性(single nucleotide polymorphism,SNP)是导致帕金森病(Parkinson′s disease)发生的遗传因素之一,但受不同种族和地域的影响.通过联合使用引物重叠PCR定点突变,限制性长度多态性分析(restriction fragment length polymorphism,RFLP)筛查了帕金森病的重要致病基因Leucine-Rich Repeat kinase 2(LRRK2)的突变体:rs34778348:G>A(G2385R);用毛细管电泳(capillary electrophoresis,CE)技术进行验证.在237个散发性帕金森病人和190个对照者中虽然未发现rs34778348:G>A的纯合子突变,但存在rs34778348:G>A的杂合子突变,并且统计分析显示病例组与对照组rs34778348:G>A的等位基因频率(p=0.010)和基因型频率(p=0.001)差异显著.显示筛查到rs34778348:G>A可能是中国散发帕金森病易感性的风险因子.该方法有助于促进帕金森病分子诊断的临床普及.
Parkinson's disease (PD) is a degenerative disorder of central nerve system (CNS),genetically attributed by known mutations of leucine-rich repeat kinase (LRRK2),alpha-synuclein (SNAC),PTEN-induced putative kinase 1 (PINK1)etc.Single nucleotide polymorphism (SNP),rs34778348:G〉A (G2385R) in LRRK2 is the most common known cause of about 5 % familiar and 3 % sporadic PD in Europe.In this study,site-specific mutation primer overlapping PCR,restriction fragment length polymorphism (RFLP) and capillary electrophoresis (CE) were applied to systematically analyze the risk factor,rs34778348:G〉A,from 237 sporadic PD patients and 190 normal Chinese.24 heterozygous SNP carriers out of 237 (10.1%) PD patients and 4 heterozygous SNP carriers out of 190 (2.1%) controls were significantly detected with p value of 0.001 and 0.010 of genotype and allele frequency,respectively.It implies that rs34778348:G〉A in LRRK2 is a potential risk factor of PD in Chinese population.Furthermore,we established the positive control of rs34778348:G〉A and mutation diagnostic standard operation procedures (SOPs) to promote the commercialization of molecular diagnosis in PD.
出处
《厦门大学学报(自然科学版)》
CAS
CSCD
北大核心
2013年第6期860-865,共6页
Journal of Xiamen University:Natural Science
基金
福建省科技计划项目(2012D062)