A common haplotype within the PON1 promoter region is associated with sporadic ALS.
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.
Landers
John E
JE
Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital East, Charlestown, MA, USA.
Shi
Lijia
L
Cho
Ting-Jan
TJ
Glass
Jonathan D
JD
Shaw
Christopher E
CE
Leigh
P Nigel
PN
Diekstra
Frank
F
Polak
Meraida
M
Rodriguez-Leyva
Ildefonso
I
Niemann
Stephan
S
Traynor
Bryan J
BJ
McKenna-Yasek
Diane
D
Sapp
Peter C
PC
Al-Chalabi
Ammar
A
Wills
Anne-Marie A
AM
Brown
Robert H
RH
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D015810:Linkage Disequilibrium; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA
D007527:Isoenzymes; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human