title: Association of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral sclerosis.
abstract: Amyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease causing the loss of motoneurons of the brain and the spinal cord. The etiology of ALS is still uncertain, but males are at increased risk for the disease than females. Several studies have suggested that motoneurons in ALS might be subjected to the double insult of increased DNA oxidative damage and deficiencies in DNA repair systems. Particularly, increased levels of 8-oxoguanine and impairments of the DNA base excision repair system have been observed in neurons of ALS patients. There is evidence that the Ser326Cys polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is associated with a reduced DNA repair activity. To evaluate the role of the hOGG1 Ser326Cys polymorphism in sporadic ALS (sALS), we screened 136 patients and 129 matched controls. In the total population, we observed association between both the Cys326 allele (p=0.02) and the combined Ser326Cys+Cys326Cys genotype (OR=1.65, 95% CI=1.06-2.88) and increased risk of disease. After stratification by gender, the Cys326 allele (p=0.01), both the Ser326Cys genotype (OR=2.14, 95% CI=1.09-4.19) and the combined Ser326Cys+Cys326Cys genotype (OR=2.15, 95% CI=1.16-4.01) were associated with sALS risk only in males. No significant association between the Ser326Cys polymorphism and disease phenotype, including age and site of onset and disease progression, was observed. Present results suggest a possible involvement of the hOGG1 Ser326Cys polymorphism in sALS pathogenesis.
authors.affiliation: Department of Neurosciences, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy. f.coppede@geog.unipi.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lo Gerfo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Carlesi
authors.forename: Selina
authors.initials: S
authors.lastname: Piazza
authors.forename: Anna
authors.initials: A
authors.lastname: Rocchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Petrozzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Nesti
authors.forename: Dario
authors.initials: D
authors.lastname: Micheli
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacci
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
authors.forename: Luigi
authors.initials: L
authors.lastname: Murri
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
mesh_terms: D000367:Age Factors; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003545:Cysteine / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012694:Serine / Q000235:genetics; D012737:Sex Factors
chemical_list: D005819:Genetic Markers; D012694:Serine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003545:Cysteine