Risk Factors And Clinical Features And Polymorphism Of ATP13a2 Gene In Patients With Parkinson’s Disease In Xinjiang

Objectives: 1. To investigate the risk factors of Sporadic Parkinson’s disease(SPD) in Xinjiang, and to analyse the difference between Uygur and Han in the risk factors of SPD. 2. To investigate the clinical symptoms of SPD in Xinjiang, and to analyse the related factors influencing the cognitive function, sleep quality and mood in SPD, and to compare the difference between Uygur and Han in clinical symptoms. 3. To investigate the polymorphism of subtypes Thr12 Met and Ala1144 Thr of ATP13A2 gene, and analyse the difference between Uygur and Han in the polymorphism in Xinjiang. Methods: 1. Analysis of the risk factors of SPD in Xinjiang: 400 cases of SPD patients as PD group,(including 210 cases of Han, and 190 cases of Uygur), and 400 cases of healthy adults as control group(including 202 cases of Han, and 198 cases of Uygur), were enrolled into the study. All of the participants were asked to finish the questionnaires, such as the basic information, the generalized anxiety scale-7(GAD-7), the patient health questionnaire depression scale-9(PHQ-9), the Montreal cognitive assessment scale(Mo CA), Pittsburgh sleep quality index(PSQI), and to be taken fasting venous blood sample for detecting glucose(FBG), triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), low density lipoprotein cholesterol(LDL-c), uric acid(UA), homocysteine(Hcy) and C-reactive protein(CRP), the risk factors of SPD were analysed and the difference was compared between Uygur and Han in the risk factors. 2.Analysis of clinical symptoms of SPD in Xinjiang: the sample of the study was the same as the above, however, two questionnaires were adds, the Unified Parkinson’s disease Rating Scale(UPDRS) and Hoehn & Yahn(H-Y) scale, and the non-motor symptoms rating scale, It was evaluated that the feature of clinic symptoms and the influence factors of cognitive function, sleep quality and mood in SPD in Xinjiang, the difference of clinic symptoms was compared between Uygur and Han. 3. Analysis of polymorphism of ATP13A2 gene in SPD in xinjiang: 420 cases of SPD patients as PD group(inciuding 220 cases of Han SPD and 200 cases of Uygur SPD), and400 cases of healthy adults as control group(including 202 casesof Han and 199 cases of Uygur) were enrolled in the study.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and gene sequencing were used to analyse the polymorphism of Thr12 Met locus of ATP13A2 gene, and polymerase chain reaction(PCR) combining DNA direct sequencing were used to analyse the polymorphism of Ala1144 Th site of ATP13A2 gene. The gene polymorphismof Thr12 Met and Ala1144 Thr sites were compared between Uygur and Han. Results: 1.Compared to the control group, the rates of alcohol consumption and pesticide exposure were higher(17.00 % vs 34.25% and 4.75 % vs 12.25%, P<0.05), and the rates of smoking, tea and coffee intaking were lower(43.25 % vs 20.25%, 63.00% vs 29.25% and 11.50% vs 6.75%, P<0.05) in PD group. Compared to the Han, the rates of history of smoking and alcohol consumption were lower(13.25% % vs 7% and 22.25 % vs 12.00%, P<0.05), and rates of history of tea intaking was higher(11.25% % vs 18%, P<0.05) in Uygur in PD group.There was no significant difference in the coffee intaking and pesticide exposure between Uygur and Han in SPD(P>0.05). 2. Compared to control group, the levels of TG, LDL-c and UA were decreased(2.52±0.99 vs 1.97±0.88, 2.78±0.65 vs 2.26±0.62 and 361.80±96.24 vs 328.11±90.80, P<0.05), Hcy was increased(8.90±4.49 vs13.78±5.48, P<0.05) in PD group. Compared to the Han, the levels of TG and LDL-c were increased(1.86±0.87 vs 2.07±0.89, 2.06±0.62 vs 2.46±0.62, P<0.05) in Uygur PD group. There were no significant differences in the levels of TC、FBG、HDL-c、UA、Hcy and CRP in SPD between Uygur and Han(P>0.05). 3.There were no significant differences in the onset symptom, onset age, course of disease, UPDRS(I, II and III sections) and H-Y scale between Uygur and Han in SPD(P>0.05). 4. Cognitive dysfunction, anxiety, depression, constipation and fatigue were the most common non-movement symptoms in SPD.Compared to the Han, constipation and fatigue were more severe in Uygur in SPD(P<0.05). 5. The onset of SPD were positively correlated with the histories of alcohol consumption and pesticide exposure, the levels of Hcy, PHQ-9 and PSQI scores(beta=0.869, 0.768, 0.975, 1.147 and 2.068, respectively), and negatively correlated with the histories of smoking, tea and coffee intaking, and the levels of TG, LDL-c, and UA(beta=-0.861,-2.613,-1.134,-2.155,-1.171 and-2.914, respectively). 6. Compared to control group, the rate of abnormal result was higher in PD group in Mo CA, PSQI, PHQ-9 and GAD-7 scores(5.75% vs 59.50%, 6.25% vs 27.25%, 7.50% vs45.50%, 7% vs58.25%, P<0.05). The score of Mo CA was negatively correlated with duration of the disease, body weight and PHQ-9 score(beta=-0.833,-0.183 and-0.330, respectively).The score of PSQI was positively correlated with age, duration of the disease and PHQ-9 score(beta=0.718, 0.718 and 0.156, respectively); The score of PHQ-9 was positively correlated with GAD-7 score(beta=0.631), and negatively correlated with the level of UA(beta=0.212). There was no significant difference between Uygur and Han in SPD in the scores and rates of abnormal result in Mo CA, PSQI, PHQ-9 and GAD-7(P>0.05).7.The mutation rates of Thr12 Met and Ala1144 Thr sites of ATP13A2 gene were 0.48%(2/420) and 0.24%(1/420), respectively. There was no significant difference(P>0.05) in polymorphism of Thr12 Met and Ala1144 Thr sites of ATP13A2 gene between PD group and control group, between two ethnics, between genders, between early-onset PD and late-onset PD. Conclusion: 1. The histories of smoking, tea and coffee intaking are protective factors of SPD.The histories of alcohol consumption and pesticide exposure, the decreased levels of TG, LDL-c and UA, the increased level of Hcy, sleep disorder and depression are risk factors of SPD.There is significant difference between Uygur and Han in SPD in the histories of smokingand tea intaking, the history of alcohol consumption, the levels of TG and LDL-c. 2. The cognitive function is correlative with the duration of the disease, BMI and depression.Sleep disorder is correlative with age, the duration of disease and depression.Depression is correlative with anxiety and the level of UA.There is significant difference between Uygur and Han in SPD in constipation and fatigue. 3. The mutation rates in subtype Thr12 Met and Ala1144 Thr of ATP13A2 gene are extremely low in SPD in Xinjiang.There is no significant difference between Uygur and Han in SPD in the polymorphism of these two sites.