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.
BACKGROUND: The humanparaoxonase (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 PON1Q192R, PON1L55M, and PON2C311S 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.
Authors: Nicola Ticozzi; Ashley Lyn LeClerc; Pamela J Keagle; Jonathan D Glass; Anne-Marie Wills; Marka van Blitterswijk; Daryl A Bosco; Ildefonso Rodriguez-Leyva; Cinzia Gellera; Antonia Ratti; Franco Taroni; Diane McKenna-Yasek; Peter C Sapp; Vincenzo Silani; Clement E Furlong; Robert H Brown; John E Landers Journal: Ann Neurol Date: 2010-07 Impact factor: 10.422
Authors: Silke Schmidt; Kelli D Allen; Valerie T Loiacono; Barbara Norman; Catherine L Stanwyck; Kristina M Nord; Christina D Williams; Edward J Kasarskis; Freya Kamel; Valerie McGuire; Lorene M Nelson; Eugene Z Oddone Journal: Neuroepidemiology Date: 2008-04-18 Impact factor: 3.282
Authors: John E Landers; Lijia Shi; Ting-Jan Cho; Jonathan D Glass; Christopher E Shaw; P Nigel Leigh; Frank Diekstra; Meraida Polak; Ildefonso Rodriguez-Leyva; Stephan Niemann; Bryan J Traynor; Diane McKenna-Yasek; Peter C Sapp; Ammar Al-Chalabi; Anne-Marie A Wills; Robert H Brown Journal: Amyotroph Lateral Scler Date: 2008-10