LRRK2 is not a Significant Cause of Parkinson's Disease in French-Canadians

Abstract

An old founder mutation (G2019S) was found with high frequency in the North African Arabs (30%) and Ashkenazi Jews (18% ). Demonstrate if mutations in the LRRK2 gene are a significant cause of Parkinson's disease (PD) in the French-Canadian founder population. Cases were recruited through a designated movement disorder clinic in Quebec City. Every index case had to meet the Ward and Gibb criteria for PD. Controls consisted of a non-disease group of similar age and ethnicity as the cases. Exons 31 and 41 of LRRK2 were amplified by PCR with intronic primers in all 125 PD cases and directly sequenced on an ABI 3700 sequencer. Six single nucleotide polymorphism were typed in 125 PD cases and 95 normal controls. Associations between unrelated cases and matched controls were analyzed. Single marker analysis and haplotype association tests were performed. Sequencing analysis did not reveal any reported or novel mutations in exons 31 and 41 of LRRK2. The G2019S mutation as well as mutations affecting amino acid 1441 were absent in the 125 patients. The case-control association study performed to detect the presence of a common variant in LRRK2 did not provide any positive signal. Single-marker and haplotype analyses systematically gave non-significant P values. We performed a case-control association study in 125 French-Canadian (FC) patients with PD and 95 FC controls and found that common variants in LRRK2 are unlikely to be a significant cause of late-onset PD in this founder population.