title: LRRK2 G2385R variant carriers of female Parkinson's disease are more susceptible to motor fluctuation.
abstract: The relation between the LRRK2 mutation and its effect on Parkinson's disease (PD) has always caught a lot attention. Recent studies found that the G2385R polymorphism of LRRK2 may increase the risk of PD in Asian populations. Here we tried to clarify the relationship between the LRRK2 G2385R variant and the clinical profiles including motor complication in Chinese PD patients. We identified the LRRK2 variant in the Chinese Han population in northern China and evaluated the relationship between the G2385R variant and clinical profiles through comparison between 36 carriers and 139 non-carriers. We found that G2385R carriers scored significantly higher in motor fluctuation and dyskinesia than non-carriers. Logistic regression analysis showed that the G2385R variant was an independent risk factor for motor fluctuation in females (odds ratio = 12.538, 95 % CI 2.216-70.942, P = 0.004), and a Chi-squared test showed that the frequency of dyskinesia tended to be higher in the carrier group compared to the non-carrier group (16 vs. 4.4 %, P = 0.050, OR = 4.127, 95 % CI 1.074-15.864). These findings indicate that the variant was closely related to the occurrence of motor complication. Additionally, the G2385R variant was significantly related to the early-onset of PD in female carriers (20.0 vs. 1.5 %, odds ratio = 16.25, 95 % CI 1.557-169.618, P = 0.020). Our study found that the G2385R variant was significantly associated with motor complications and that this variant was an independent risk factor for motor fluctuation in females. These findings provide the necessary preliminary data to better understand the unique profile of PD G2385R variant carriers.
authors.affiliation: Neurology Department of First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.forename: Hao
authors.initials: H
authors.lastname: Pang
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
authors.forename: Zhi-Yi
authors.initials: ZY
authors.lastname: He
mesh_terms: D000368:Aged; D005260:Female; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D012720:Severity of Illness Index; D012737:Sex Factors; D018709:Statistics, Nonparametric
chemical_list: D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine
references.citation: Parkinsonism Relat Disord. 2013 Mar;19(3):397-8
references.pmid: 22981185
references.citation: Mov Disord. 2007 Aug 15;22(11):1640-3
references.pmid: 17523199
references.citation: Endocrine. 2003 Jun;21(1):81-7
references.pmid: 12777707
references.citation: Mov Disord. 2009 Jul 15;24(9):1359-65
references.pmid: 19424986
references.citation: Parkinsonism Relat Disord. 2010 Feb;16(2):85-8
references.pmid: 19854095
references.citation: Mov Disord. 2007 Sep 15;22(12):1816-8
references.pmid: 17659642
references.citation: Transl Neurodegener. 2012 May 31;1(1):11
references.pmid: 23211054
references.citation: Mov Disord. 2007 Oct 15;22(13):1901-11
references.pmid: 17674410
references.citation: Parkinsonism Relat Disord. 2007 Mar;13(2):89-92
references.pmid: 17222580
references.citation: Mov Disord. 2009 May 15;24(7):1034-41
references.pmid: 19343804
references.citation: Neurogenetics. 2006 Jul;7(3):133-8
references.pmid: 16633828
references.citation: Neurol Sci. 2013 Nov;34(11):2001-6
references.pmid: 23624603
references.citation: Mov Disord. 2007 Dec;22(16):2439-43
references.pmid: 17960808
references.citation: J Neural Transm (Vienna). 2008 Sep;115(9):1275-7
references.pmid: 18523722
references.citation: Neurology. 1990 Oct;40(10):1529-34
references.pmid: 2215943
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2009 Oct 5;150B(7):1022-3
references.pmid: 19152345
references.citation: J Neurol. 2009 Mar;256(3):483-7
references.pmid: 19412725
references.citation: Am J Epidemiol. 2004 Nov 15;160(10):977-84
references.pmid: 15522854
references.citation: Neurogenetics. 2008 Oct;9(4):263-9
references.pmid: 18704525
references.citation: Hum Genet. 2007 Feb;120(6):857-63
references.pmid: 17019612
references.citation: J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
references.pmid: 1564476
references.citation: Neurology. 2003 Mar 11;60(5):790-5
references.pmid: 12629235
references.citation: BMC Neurol. 2006 Dec 22;6:47
references.pmid: 17187665
references.citation: Eur J Neurol. 2008 Mar;15(3):301-5
references.pmid: 18201193
references.citation: Neurology. 2008 Jan 15;70(3):200-9
references.pmid: 17761549