title: Increased incidence of FMO1 gene single nucleotide polymorphisms in sporadic amyotrophic lateral sclerosis.
abstract: Flavin-containing monooxygenases (FMO) represent a gene family involved in the oxidative metabolism of a variety of xenobiotics, pesticides and drugs. A new function for FMO proteins has been recently uncovered: yeast FMO has been demonstrated to take part in maintaining the redox balance, catalysing the oxidation of reduced glutathione (GSH) to glutathione disulfide (GSSG). The GSSG/GSH balance is an important buffering system for reactive oxygen species and its involvement has been documented in ALS and other neurodegenerative disorders. Human FMO genes present different mutations, which may be related to ethnicity, altered metabolic activity and, in some cases, specific diseases. The human FMO1 gene presents 20 single nucleotide polymorphisms (SNPs) located in coding regions, intronic sequences and untranslated regions. The FMO1 gene has also recently been found underexpressed in spinal cord of ALS patients. Using SSCP and direct sequencing, we studied the allelic and genotypic frequency of two 3'UTR SNPs of the FMO1 gene in sporadic ALS patients compared to a healthy control population. We found a significantly higher frequency of these two polymorphisms, exclusive of the female population, in SALS patients compared to controls (p<0.01), suggesting that specific allelic variants of the FMO1 gene might be associated to susceptibility to develop ALS.
authors.affiliation: Experimental Neurobiology, Neurological Institute IRCCS C Mondino, Pavia, Italy. cristina.cereda@mondino.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.forename: Elisa
authors.initials: E
authors.lastname: Gabanti
authors.forename: Manuel
authors.initials: M
authors.lastname: Corato
authors.forename: Annalisa
authors.initials: A
authors.lastname: de Silvestri
authors.forename: Dario
authors.initials: D
authors.lastname: Alimonti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cova
authors.forename: Andrea
authors.initials: A
authors.lastname: Malaspina
authors.forename: Mauro
authors.initials: M
authors.lastname: Ceroni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010105:Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)