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A common haplotype within the PON1 promoter region is associated with sporadic ALS

journal contribution
posted on 2023-06-08, 13:41 authored by John E Landers, Nigel LeighNigel Leigh, Lijia Shi, Jonathan D Glass, Christopher E Shaw, Frank Diekstra, Meraida Polack, Ildefonso Rodriguez-Leyva, Stephan Niemann, Bryan J Traynor, Diane McKenna-Yasek, Peter C Sapp, Ammar Al-Chalabi, Anne-Marie A Wills, Robert H Brown Jr
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.

History

Publication status

  • Published

Journal

Amyotrophic Lateral Sclerosis

ISSN

1471-180X

Publisher

Taylor & Francis

Issue

5

Volume

9

Page range

306-314

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-11-14

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