2011
DOI: 10.1016/s1474-4422(11)70175-2
|View full text |Cite|
|
Sign up to set email alerts
|

Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case–control study

Abstract: Background Leucine-rich repeat kinase 2 (LRRK2) is known to harbor highly penetrant mutations linked to familial parkinsonism. However, its full polymorphic variability in relationship to Parkinson’s disease (PD) risk has not been systematically assessed. Methods We examined the frequency pathogenicity of 121 exonic LRRK2 variants in three ethnic series (Caucasian [N=12,590], Asian [N=2,338] and Arab-Berber [N=612]) consisting of 8,611 patients and 6,929 control subjects from 23 separate sites of the Genetic… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

17
281
6
1

Year Published

2014
2014
2023
2023

Publication Types

Select...
6
2

Relationship

0
8

Authors

Journals

citations
Cited by 301 publications
(305 citation statements)
references
References 33 publications
17
281
6
1
Order By: Relevance
“…18 Common variants in MAPT are an established risk factor for PD 3,4 and the relevance of allelic series -that is, both common variants of weak effect and rare variants of strong effect in one gene -to PD has already be shown. 4,19 Yet, in our sample, rare variants in APP, not MAPT, were enriched in PD. However, since a physical interaction between MAPT and APP and a role of MAPT in trafficking APP to the cell membrane has been reported, 18,20 rare variants in APP could have a similar effect with regard to PD as MAPT variants.…”
Section: Discussionmentioning
confidence: 48%
“…18 Common variants in MAPT are an established risk factor for PD 3,4 and the relevance of allelic series -that is, both common variants of weak effect and rare variants of strong effect in one gene -to PD has already be shown. 4,19 Yet, in our sample, rare variants in APP, not MAPT, were enriched in PD. However, since a physical interaction between MAPT and APP and a role of MAPT in trafficking APP to the cell membrane has been reported, 18,20 rare variants in APP could have a similar effect with regard to PD as MAPT variants.…”
Section: Discussionmentioning
confidence: 48%
“…Among these, the coding variants G2385R in the WD40 domain and R1628P in the COR domain act as common PD risk factors among Asian populations 44, 45, 46. The G2385R variant essentially doubles the lifetime risk of getting PD 47. It has been shown that the C‐terminally truncated constructs that include the WD40 domain impacts on LRRK2 kinase activity, and a G2385R substitution resulted in ~ 50% loss of kinase activity 13.…”
Section: Lrrk2 Genetics Protein Domain Structure; Kinase and Gtpase mentioning
confidence: 99%
“…The genome‐wide association study by Ross et al . 47 showed the LRRK2 locus to be an independent risk factor for sporadic PD. This important finding, together with a similar phenotypic spectrum of LRRK2 patients compared with sporadic cases 51, has fuelled the hypothesis that LRRK2 might also play a role in the pathogenesis of sporadic PD.…”
Section: Lrrk2 Genetics Protein Domain Structure; Kinase and Gtpase mentioning
confidence: 99%
“…Two variants in LRRK2 that are predominantly found in Asian populations, G2385R [93][94][95][96][97] and R1628P [98][99][100][101], increase the lifetime risk of PD about 2-fold [102]. Molecular modeling predicts that the G2385 residue is located on the outer surface of the WD40 domain towards the C-terminus of LRRK2 [31].…”
Section: Genetic Risk Factors Associated With Parkinson's Diseasementioning
confidence: 99%
“…The R1398H LRRK2 polymorphism is quite common (>5 %) in several populations and apparently plays a protective role against development of PD [102,[106][107][108][109]. The R1398 residue is located in the switch II motif of the ROC domain and could be important for the interaction with the γ-phosphate of GTP [87].…”
Section: Lrrk2 Polymorphisms That May Affect Protein Functionmentioning
confidence: 99%