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From the Departments of Neurology (A.S., B.T., D.P., W.T., J.P., T.D., A.Sz.), Pharmacology (P.P.W.), and Metabolic Diseases (M.T.M.), Jagiellonian University, Krakow, Poland and Department of Neurology (D.A.F.), University of Michigan, Ann Arbor, MI.
Address correspondence and reprint requests to Dr. Agnieszka Slowik, Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland; e-mail: slowik{at}cm-uj.krakow.pl
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.
Editorial, see page 738
See also page 771
This article was previously published in electronic format as an Expedited E-Pub on July 5, 2006, atwww.neurology.org.
Supported by grant no. 2PO5B 014 26 from the Polish State Committee for Scientific Research. D.A.F. is supported by NIEHS/NIH and MDA-USA.
Disclosure: The authors report no conflicts of interest.
Received July 13, 2005. Accepted in final form March 17, 2006.
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