LRRK2 gene G2019S mutation and SNPs [haplotypes] in subtypes of Parkinson's disease

Document Type

Article

Abstract

Mutation within the leucine-rich repeat kinase 2 (LRRK2) gene has been identified as a cause of autosomal dominant Parkinson's disease (PD). The purpose of this study was to determine the frequency of G2019S mutation and whether the differences in the allele and genotype distribution of six SNPs within LRRK2 gene are associated with PD in an American non-Hispanic white population. The sample included 350 sporadic PD (SPD), 225 familial PD (FPD) patients and 186 controls of the same race and ethnicity. The frequency of LRRK2 G2019S mutation in our total sample of PD (FPD and SPD) was 1.56%. The frequency of this mutation was 3.5% in the FPD and 0.3% in the SPD groups, respectively. Allele and genotype frequencies of six SNPs were compared between PD and control samples. In addition, PD groups were categorized by sporadic PD (no family history), familial PD (first degree relative with PD) and age of onset (AON, or=51years). The haplotypes of the six SNPs were also constructed for association analysis. After correction for multiple comparisons, there was no association between any SNPs (allele or genotype) and PD groups. One of the haplotypes was modestly associated with the combined PD (SPD and FPD) sample. There was also no association with age at onset of PD. Our study suggests that the LRRK2 gene may be a risk factor or the cause for a very small fraction of PD in American white population.

Medical Subject Headings

Age of Onset; Aged; Aged, 80 and over; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Glycine (genetics); Haplotypes; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Male; Middle Aged; Parkinson Disease (classification, genetics); Polymorphism, Single Nucleotide (genetics); Protein Serine-Threonine Kinases (genetics); Serine (genetics); Whites

Publication Date

3-1-2009

Publication Title

Parkinsonism & related disorders

ISSN

1353-8020

Volume

15

Issue

3

First Page

175

Last Page

80

PubMed ID

18752982

Digital Object Identifier (DOI)

10.1016/j.parkreldis.2008.05.004

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