Paraoxonase gene polymorphisms and sporadic ALS.
BACKGROUND
The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, located adjacent to each other on chromosome 7. PON catalytic activity may be influenced by frequent amino acid variants. Chronic exposure to certain chemicals or to environmental factors causing enhanced lipid peroxidation metabolized by paraoxonases may be a risk factor for sporadic ALS (sALS).


OBJECTIVE
The aim of this study was to examine the association between PON1 Q192R, PON1 L55M, and PON2 C311S functional polymorphisms and the risk of sALS in a Polish population.


METHODS
The authors included 185 patients with a definite or probable diagnosis of sALS (El Escorial Criteria) and 437 healthy controls of similar age and gender. The paraoxonase polymorphisms were studied by PCR and restriction enzyme digestion.


RESULTS
Using logistic regression analyses, the C allele of the C311S polymorphism was associated with sALS in dominant and additive models, whereas the R allele of the Q192R polymorphism was associated with sALS in recessive, additive, and dominant models. The authors compared the distribution of haplotypes between cases and controls. The R-C haplotype was overrepresented among cases (odds ratio 3.44, 95% CI: 1.55 to 7.62, p = 0.002).


CONCLUSIONS
Frequent amino acid variants in the paraoxonase 1 and paraoxonase 2 genes are associated with sporadic ALS in a Polish population.
Slowik
A
A
Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland. slowik@cm-uj.krakow.pl
Tomik
B
B
Wolkow
P P
PP
Partyka
D
D
Turaj
W
W
Malecki
M T
MT
Pera
J
J
Dziedzic
T
T
Szczudlik
A
A
Figlewicz
D A
DA
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D012694:Serine / Q000235:genetics
D005973:Glutamine; D012694:Serine; D001120:Arginine; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C468411:PON2 protein, human; D003545:Cysteine