Clinical Phenotype Analysis Of Parkinson's Disease Associated With LRRK2 Variants In Chinese Han Population

Objective:Parkinson's disease(PD)is a common neurodegenerative disease.LRRK2 is commonly implicated in both familial and sporadic PD.The polymorphic variants G2385R and R1628P have been associated with a significantly increased risk of developing PD in various Asian populations.Different variants may have different phenotypes and it is important to understand the phenotype of LRRK2 variants.Our study aimed to compare motor and non-motor symptoms,imaging features of patients with PD who are carriers of the leucine-rich repeat kinase 2(LRRK2)gene variants(LRRK2-PD)and patients with idiopathic PD(IPD).Methods:Three hundred fifty-six patients with PD were enrolled in our study.Demographic information was collected.Unified Parkinson's Disease Rating Scale(UPDRS)and Hoehn and Yahr(H-Y)stage scale were also performed.The Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA),Hamilton Anxiety Scale(HAMA),Hamilton Rating Scale for Depression(HRSD)and the non-motor symptoms questionnaire(NMSQ)were applied to evaluate non-motor symptoms.Peripheral blood samples were collected and DNA was extracted for next generation sequencing.PD patients were devided into LRRK2-PD and IPD.LRRK2-PD included PD with common LRRK2 variants(common LRRK2-PD)and PD with G2385R variant(G2385R-PD).Among the 356 patients,236 underwent transcranial sonography(TCS).The area of bilateral substantia nigra,midbrain area,width of the third ventricle,echo of pisciform nucleus and raphe nucleus were recorded.Results:There were 90 patients carring LRRK2 variants,including 60 common LRRK2 carriers and 55 G2385R carriers.LRRK2-PD(n=90)and non-carriers(n=266)were similar in age,age at onset,gender,course of disease,UPDRS ?,?,?,? scores,MMSE score,MoCA score,HAMA score,HRSD score and NMSQ score.Common LRRK2-PD and G2385R-PD were same as LRRK2-PD in terms of above characteristics.Common LRRK2-PD showed higher H-Y stage than IPD.All carriers were more likely to have hyposmia(67.1%vs 51.7%,P=0.011;68.6%vs51.7%,P=0.027;70.2%vs 51.7%,P=0.020;49.2%vs 31.0%,P=0.011).There was no significant difference between the two groups in terms of TCS parameters.Conclusions:G2385R variant is the most common LRRK2 variantOmi/HtrA2 in Parkinson's disease,Human Molecular Genetics,14(2005)2099-2111.in Chinese Han population.PD with LRRK2 variants is similar to IPD as to motor,non-motor symptoms and imaging features of TCS,but characterized by more hyposmia.