Research On Mutations Of LRRK2 Gene And VPS35 Gene In PD Patients

Objective To investigate the VPS35 p Asp620Asn,LRRK2G385 R,R1628P and R1441G/C/H genetic polymorphisms with sporadic PD patients and normal control group in Tianjin Han population,aim to understand the distribution of these gene polymorphisms in Tianjin Han population, and to analyze the clinical phenotypes of sporadic PD patients carrying LRRK2 mutation or no mutations, in order to distinguish the two genetypes according to its phenotype.Methods We conducted a case-control study, including 217 sporadic PD patients and 192 healthy controls. The sporadic PD patients were given detailed clinical investigations and physical examinations. We applied SNa Pshot to detect the genetic varients.The correlations between these SNPs and PD were analyzed respectively.The data was analyzed by SAS9.3 software.Results 1 In the detection of G2385 R,33 PD patients have G2385R(15.21%),32 PD patients were CT genotype(14.75%),1 PD patients were TT genotype(0.46%), significantly higher than that of the six cases of CT genotype(3.13%)( P<0.05,OR=5.361,95%CI=2.19-13.24).The PAR% of approximately 6.27% was gained. Stratified the age: Late-onset PD Patients and the corresponding age group have significant difference(p<0.05,OR=5.529,95%CI:2.083-14.626),however early-onset PD Patients and the corresponding age group have no significant difference(p>0.05,OR=4.522,95%CI:0.471-43.417). LRRK2G2385 R associates with late-onset PD. 2.In the detection of R1628 P,3 PD patients were GC genotype(1.38%)and 1 case control was GC genotype. There was no significant difference between the two groups(p>0.05). 3. In the detection of LRRK2R1441 H, there was only 1 case of R1441 H mutation, and the case carring G2385 R mutation while there were no these mutations detected in the control group.4. In the detection of LRRK2R1441G/C,there was none this genoype detected both in PD group and the control group. 5. The PD patients carrying the LRRK2G2385 R were no statistically significant differences in age, sex, duration of disease, mode of onset, clinical symptoms, the response to levodopa, imaging, H-Y grade and MMSE score with no carrying mutation. 6. In the detection of VPS35Asp620 Asn, there was none this genetype detected both in PD group and the control group.Conclusions 1. LRRK2 gene G2385 R mutation in Tianjin Han population associates only with late-onset Parkinson disease. 2. LRRK2 gene R1628 P mutation in Tianjin Han population does not associate with Parkinson disease. 3. There is no R1441C/G mutations in Chinese Han population. LRRK2R1441 H is a rare mutation locus in Chinese Han population. 4. Carrying the LRRK2G2385 R does not impact on clinical phenotypes of PD patients. 5. Tianjin Han population does not or rarely carry VPS35 mutation genetype.