1. A common haplotype within the PON1 promoter region is associated with sporadic ALS
- Author
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Anne-Marie Wills, Ting-Jan Cho, Peter C. Sapp, John Landers, Diane McKenna-Yasek, Jonathan D. Glass, Lijia Shi, Ammar Al-Chalabi, Frank P. Diekstra, Christopher Shaw, Stephan Niemann, Meraida Polak, Ildefonso Rodriguez-Leyva, Bryan J. Traynor, P. Nigel Leigh, and Robert H. Brown
- Subjects
haplotypes ,Linkage disequilibrium ,Genotype ,SNP ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Gene cluster ,medicine ,Humans ,Genetic Predisposition to Disease ,Amyotrophic lateral sclerosis ,Promoter Regions, Genetic ,Genetics ,biology ,Aryldialkylphosphatase ,case-control studies ,Amyotrophic Lateral Sclerosis ,Haplotype ,Paraoxonase ,Sequence Analysis, DNA ,General Medicine ,medicine.disease ,PON1 ,paraoxonase ,Isoenzymes ,Neurology ,Multigene Family ,biology.protein ,Original Article ,Neurology (clinical) ,Age of onset - Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder of upper and lower motor neurons. Genetic variants in the paraoxonase gene cluster have been associated with susceptibility to sporadic ALS. Because these studies have yielded conflicting results, we have further investigated this association in a larger data set. Twenty SNPs spanning the paraoxonase gene cluster were genotyped on a panel of 597 case and 692 control samples and tested for association with risk of sporadic ALS and with ALS sub-phenotypes. Our study revealed two SNPs, rs987539 and rs2074351, within the paraoxonase gene cluster that are associated with susceptibility to sporadic ALS (uncorrected p=6.47E-04 and 7.87E-04, respectively). None of the 20 SNPs displayed significant associations with age of onset, site of onset or disease survival. Using a sliding window approach, we have also identified a 5-SNP haplotype that is significantly associated with risk of sporadic ALS (p=2.75E-05). We conclude that a common haplotype within the PON1 promoter region is associated with susceptibility to sporadic ALS.
- Published
- 2008