摘要
目的 探讨parkin基因启动子区 - 2 5 8T/G多态性位点与帕金森病 (Parkinson’sdisease,PD)的相关性 ,尤其是该多态与PD发病年龄的关系。方法 应用聚合酶链反应 (PCR)、变性高效液相和测序等方法分析parkin基因 - 2 5 8T/G多态性位点在PD患者和健康对照间分布频率的差异。结果 检测了 2 99例PD患者和 15 6名健康对照。总体分析发现 ,PD组G等位基因频率和T/G +G/G基因型频率高于对照组 ,但差异无显著意义。将PD组按年龄分层后 ,6 0岁以上PD患者parkin基因 -2 5 8T/G多态G等位基因频率 (5 6 6 % )明显高于健康对照组 (4 2 6 % ) ,OR =1 76 ,95 %CI为 1 15～2 6 9(P =0 0 0 6 4 ) ,而 6 0岁以下发病者与对照相比差异无显著意义。相应的基因型频率 (T/G +G/G)在 6 0岁以上发病PD组为 80 9% ,对照组为 6 9 9% ,两者虽未达统计学差异 ,但PD组明显高于对照组。OR =1 82 ,95 %CI为 0 87～ 3 88。年龄分层后的趋势分析显示相对危险度与PD发病年龄间存在正相关联系。结论 研究结果证实 - 2 5 8T/G多态可能是中国人晚发PD的一个危险因素。
Objective To investigate the association between the -258T/G polymorphism in the promoter of parkin gene and the risk for Parkinson’s disease (PD) in Chinese, particularly in relation to the age of onset of PD patients. Methods PD was diagnosed according to the criteria of CAPIT (core assessment program for intracerebral transplantations). All patients and controls were examined by two neurologists and were of Han ethnical origin. Polymerase-chain-reaction(PCR), denaturing high performance liquid chromatography (dHPLC) and sequencing were used to determine the genotype of each subject. Results A total 299 PD patients and 156 controls, including 143 early-onset PD (EOPD) patients with an onset of symptoms below 50, and 156 late-onset PD (LOPD) patients with an onset age at or older than 50, were studied. Chi-square analysis revealed that the frequencies of the G allele and T/G+G/G genotypes were higher in total PD group than in control group (P = 0.068 and 0.282, respectively). After being stratified by onset age, the frequency of the G allele was significantly high (OR=1.76, 95% CI: 1.15-2.69, P=0.0064) in patients with an onset age over 60 years (56.6%) than that in the control group (42.6%). The linear trend analysis showed that the G allele was increased significantly in the PD group with an increasing onset age (χ 2=6.775, P=0.0092). Similarly, the frequency of T/G+G/G genotypes was much higher (OR=1.82, 95%CI: 0.87～3.88) in the older onset group (80.9%) than that in the control group (69.9%), although the difference was not statistically significant. On the other hand, there was no difference in the frequencies of allele and genotype between the younger onset PD patients and the controls. Conclusion Our results suggest that the parkin promoter -258T/G polymorphism might be a genetic risk factor for LOPD in Chinese.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2004年第2期122-125,共4页
Chinese Journal of Neurology
基金
北京市自然科学基金资助项目 ( 70 3 10 0 2 )
北京市卫生局重点学科资助项目 ( 1998卫科扶字 12号 )
北京市卫生局首都发展基金 ( 2 0 0 2 3 0 11)
北京市科委项目 ( 95 5 0 2 0 5 0 0)
