浙江温州地区LRRK2基因多态性与帕金森病相关性研究

Research on Polymorphisms of LRRK Gene in Patients with Parkinson's Disease

目的探讨LRRK2基因G2385R基因型与中国沿海地区汉族人群PD相关性,分析G2385R基因型在PD发病中作用。方法收集PD患者257例和健康对照259例临床资料与基因组DNA。采用PCR-RFLP技术检测PD患者G2385R基因型;测定变异携带者及非携带者DNA序列。分析G2385R基因型在病例组和对照组中分布频率及其与性别、年龄相互作用,统计G2385R变异人群归因危险度百分比。结果 PD组25例患者GA基因型（9.7%）高于对照组6例GA基因型（2.0%）（χ2=15.57,P〈0.0001,OR=5.24,95%CI=2.11-12.99）。人群归因危险度百分比7.86%。未发现AA基因型。晚发型PD患者GA基因型为10.0%,与对应年龄对照组GA基因型2.2%有统计学差异（χ2=11.88,P=0.002,OR=4.97,95%CI=1.83-13.52）。携带G2385R患者同非携带患者临床表型在性别、发病年龄、临床症状、UPDRS评分及HoehnYahr分级均无统计学差异。结论 G2385R变异在中国沿海地区汉族人群中仅与晚发性帕金森病相关,G2385R变异与东亚人群帕金森病具有相关性,存在不同地区差异。

OBJECTIVE To explore G2385R genetype and PD of Han Chinese in littoral of Zhejiang province, then analyzed all the studies on relationship between the G2385R genetype and PD. METHODS The clinical data and extracted DNA from peripheral blood of 259 cases of PD patients and 257 healthy controls were collect- ed. Polymerase Chain Reaction combined with restriction fragment length polymorphism（PCR-RFLP）was used to de- tected the G2385R genetype of PD patients,for the G2385R genetype of line carders and non-carriers was verified by the sequencing. The distribution of genotype frequencies in 259 casesof PD patients and 257 healthy controls were compared,then the population attributable risk percent（PAR% ） of G2385R variations was count and the synergy with gender and age interaction was analyzed at the same time. RESULTS In the detection of G2385R,25 PD pa- tients were GA genotype （ 9.7% ）, significantly higher than that of the six cases of GA genotype （ 2. 0% ） （ X2 = 15.57 ,P 〈0. 0001 ,OR =5.243,95% CI：2. 115 - 12. 996）. The PAR was 7.86%. No PD patient with AA genotyp was found. The patients with late-onset PD patients ,20 cases of GA genotype （ 10. 0% ） ,corresponding to the age of the control group, 5 cases of GA genotype （2. 2% ）, both statistically significant difference （ X2 = 11. 886, P = 0. 002, OR = 4. 978,95% CI ： 1. 832-13. 523）. The aspects of clinical phenotype （ such as sex, age, clinical symptoms, UP- DRS score and Hoehn-Yahr grade）of patients carrying G2385R was not statistically different. CONCLUSION The G2385R variant in the LRRK2 gene may be a risk factor of the late-onset Parkinson＇s disease in littoral of Zhejiang province. The G2385R may result in more incidence of Parkinson＇S disease in East Asia. However,there is difference in different regions.