早发型帕金森病患者DJ-1基因突变及启动子区g．168—185del多态与帕金森病的关系

Mutation analysis of D J-1 in patients with early-onset Parkinson＇ s disease and relationship between the g. 168_185del polymorphism and Parkinson＇ s disease

目的探讨在早发型帕金森病患者（early．onsetParkinson’sdisease，EOPD）中DJ—1基因的突变情况，并分析1号内含子上再168—185del多态类型是否与帕金森病的发生有关。方法应用聚合酶链反应（PCR）结合直接测序法对90例EOPD患者进行DJ-1基因7个外显子突变分析。针对1号内含子的g．168—185del多态性，比较EOPD患者与健康人的基因型频率及等位基因频率是否存在差异。结果（1）在90例EOPD患者中没有筛查出DJ-1基因的致病性突变，但发现位于1号外显子上g．5027G〉A（rs17523802）、g．5065T〉C（rs226249）、g．5094C〉T（rs11121064）及位于1号内含子的g．168—185de14种多态类型。（2）针对爵168—185del分析，EOPD组与健康对照组插入／缺失频率分别为11．1％（10／90）和13．3％（14／105），插入／插入频率分别为88．9％（80／90）和86．7％（91／105），比较基因型频率Y值为0．222，P值为0．669；EOPD组与对照组插入型频率分别为94．4％（170／180）和93．3％（196／210），缺失型频率分别为5．6％（10／180）和6．7％（14／210），比较等位基因频率Y。值为0．207，P值为0．679；家族性EOPD组与对照组问基因型频率及等位基因频率，散发性EOPD组与对照组问基因型频率及等位基因频率差异均无统计学意义。结论本组EOPD患者中DJ-1基因的突变率较低，不是常见致病因素；g．168—185del多态位点与EOPD患者可能无直接致病关系。

Objective To evaluate the prevalence of the DJ-1 mutation in early-onset Parkinson＇ s disease （EOPD） patients, and analyzed the association between the certain polymorphic marker g. 168_ 185del in intronl and Parkinson＇ s disease （ PD）. Methods We screened all 7 exons and exon-intron boundary regions of DJ-1 by PCR and direct nucleotide sequencing in 90 Chinese patients with EOPD. We also compared the allele and genotype frequencies of the g. 168_185del polymorphism between EOPD patients and controls. Results We found no causative DJ-1 mutations in our cohort of Chinese EOPD patients. But we did identified 4 known polymorphic variants, including the g. 168_185del in intron 1, g. 5027G 〉 A （rs17523802） , g. 5065T 〉 C （ rs226249 ） , and g. 5094C 〉 T （ rs11121064 ） within exon 1. Del/Ins frequencies of the g. 168_185del polymorphism were 11.1% （10/90） and 13.3% （ 14/105 ） in EOPD group and normal group, respectively. Ins/Ins frequencies were 88.9% （80/90） and 86. 7% （91/105）, thex2 and P value of genotype frequency were 0. 222 and 0. 669 between EOPD patients and controls, respectively. The insert frequencies were 94.4% （170/180） and 93.3% （196/210） in EOPD patients and controls, the deletion frequencies were 5.6% （10/180） and 6. 7% （14/210） , thex2 and P value of allele frequency were0. 207 and 0. 679 between EOPD patients and normal, respectively. Furthermore, the P value of genotype and allele frequencies were 0. 736 and 0. 744 between familial EOPD patients and controls, respectively; P values of genotype and allele frequencies were 0. 847 and 0. 852 between sporadic EOPD patients and control group, respectively. There was no statistical difference between groups. Conclusion Mutations in DJ-I are uncommon in Chinese EOPD patients, and no association is observed between the DJ-1 intron 1 g. 168 185del polvmomhism and risk of PD.