parkin基因多态性与四川地区散发性帕金森病的相关性研究

Association analysis of the parkin gene in patients with sporadic Parkinson＇s disease from a Han population of Sichuan province

目的 了解四川地区散发性帕金森病parkin基因多态性与帕金森病（Parkinson’s disease，PD）的相关性。方法 采用病例．对照研究，应用聚合酶链反应、限制性片段长度多态性、变性高效液相色谱及DNA测序等技术，对四川地区汉族人群198例帕金森病患者和187名正常对照parkin基因-258T／G及IVS3—20T／c多态性位点进行研究，并通过比较各多态性在PD患者和正常对照人群中的频率分布，探讨基因多态性与PD的可能关系。结果 parkin基因-258T／G多态性PD组G等位基因频率明显高于对照组（52．5％vs43．3％），两组差异有统计学意义（χ^2=6．17，P〈0．025，OR=1．45，95％CI：1．04～1．86）；进一步将PD组按发病年龄分层发现，只有50岁以上发病患者与对照组相比G等位基因频率差异具有统计学意义（χ^2=9．048，P〈0．01，OR=1．57，95％CI：1．08～2．06）；同样，与对照组（69．51％）相比，PD组TG＋GG基因型频率（78．79％）亦增加，两者间差异具有统计学意义（χ^2=3．854，P〈0．05，OR=1．63，95％CI0．88～2．38）；PD组不同基因型组间发病年龄差异具有统计学意义（P〈0．05），GG基因型组的平均发病年龄比TT或TG基因型的发病晚近5年左右。parkin基因IVS3—20T／C多态性以CC基因型多见，TC型杂合子的频率较低，该实验未发现TT基因型。结论 核心启动子区-258T／G多态G等位基因可能增加了四川地区汉族人群散发性PD发生的风险，尤其是50岁以后的发病风险；四川地区汉族人群IVS3—20T／C位点，以CC基因型多见，TC型杂合子的频率较低，无TT基因型。

Objective To determine whether there are any associations between the - 258T/G polymorphism of the promoter and the IVS3 - 20T/C polymorphism in parkin gene and Parkinson＇ s disease （PD） from a Han population in Sichuan province, Methods Polymerase chain reaction （PCR）, restriction fregment length polymorphism, denaturing high performance liquid chromatography（dHPLC） and sequence analysis were used to determine the genotype of each subject. The - 258T/G polymorphism and IVS3 - 20T/C polymorphism were analysed in 198 patients with sporadic PD and 187 healthy controls, matched for age and gender. Results There were significant differences in allele frequency of the - 258T/G polymorphism between PD patients and controls, with the G allele more common in cases than controls （52.5% vs43.3%; χ^2 =6.17, P〈0.025, OR= 1.45, 95% CI 1.04-1.86）. There were also significant differences in G allele frequency between PD patients with onset age over 50 years old and controls （χ^2 =9.048,P 〈 0.01, OR = 1,57, 95 % CI： 1.08-2,06 ）. The frequency of TG ＋ GG genotype was significantly higher in PD patients than in controls （78.79% vs 69.51%; χ^2=3.854,P 〈0.05, OR= 1.63, 95% CI：0.88-2.38）. In addition, there were significant differences in age of onset between PD patients with different genotypes （ P 〈 0.05）. The average age of onset in group of GG genotype was later about 5 years compared with the group of TT or TG genctype. The frequency of CC genotype in IVS3 - 20T/C polymorphism was much higher than that of TC genotype. No TT genotype was found, Conclusion This study suggests that the parkin promoter - 258T/G polymorphism might be a risk factor for late onset PD in Sichuan. CC genotype for IVS3 - 20T/C polymorphism is common in Sichuan Han population. No TT genotype for IVS3 - 20T/C polymorphism is found in Sichuan Han population.