Introduction Previous studies have associated single-nucleotide polymorphisms (SNPs) in the gene encoding the detoxifying enzyme paraoxonase 1 (PON1) to the risk of sporadic ALS. Here, we aimed to assess the role of the coding rs662 (Q192R) SNP as a modifier of ALS phenotype. Materials and methods We genotyped a cohort of 409 patients diagnosed with ALS at our Center between 2002 and 2009 (269 males and 140 females; mean age at onset, 58.3 ± 37.5 years). Results We found PON1 to be a disease modifier gene in ALS, with the minor allele G associated both with bulbar onset (30.9% vs. 24.6%, p = 0.013) and independently with reduced survival (OR = 1.38, p = 0.012) under a dominant model. No association was found with gender or age at onset. Discussion As this SNP is known to modify the detoxifying activity of paraxonase 1 with respect to different substrates as well as other activities of the protein, we hypothesize that the identified association might reflect specific motor neuron vulnerability to certain exogenous toxic substances metabolized less efficiently by the 192R alloenzyme, or to detrimental endogenous pathophysiological processes such as oxidative stress. Further exploration of this possible metabolic susceptibility could deepen our knowledge of ALS pathomechanisms.
PON1 is a disease modifier gene in amyotrophic lateral sclerosis : association of the Q192R polymorphism with bulbar onset and reduced survival / F. Verde, C. Tiloca, C. Morelli, A. Doretti, B. Poletti, L. Maderna, S. Messina, D. Gentilini, I. Fogh, A. Ratti, V. Silani, N. Ticozzi. - In: NEUROLOGICAL SCIENCES. - ISSN 1590-1874. - (2019 Mar 22). [Epub ahead of print] [10.1007/s10072-019-03834-2]
PON1 is a disease modifier gene in amyotrophic lateral sclerosis : association of the Q192R polymorphism with bulbar onset and reduced survival
F. Verde
;C. Tiloca;B. Poletti;A. Ratti;V. Silani;N. Ticozzi
2019
Abstract
Introduction Previous studies have associated single-nucleotide polymorphisms (SNPs) in the gene encoding the detoxifying enzyme paraoxonase 1 (PON1) to the risk of sporadic ALS. Here, we aimed to assess the role of the coding rs662 (Q192R) SNP as a modifier of ALS phenotype. Materials and methods We genotyped a cohort of 409 patients diagnosed with ALS at our Center between 2002 and 2009 (269 males and 140 females; mean age at onset, 58.3 ± 37.5 years). Results We found PON1 to be a disease modifier gene in ALS, with the minor allele G associated both with bulbar onset (30.9% vs. 24.6%, p = 0.013) and independently with reduced survival (OR = 1.38, p = 0.012) under a dominant model. No association was found with gender or age at onset. Discussion As this SNP is known to modify the detoxifying activity of paraxonase 1 with respect to different substrates as well as other activities of the protein, we hypothesize that the identified association might reflect specific motor neuron vulnerability to certain exogenous toxic substances metabolized less efficiently by the 192R alloenzyme, or to detrimental endogenous pathophysiological processes such as oxidative stress. Further exploration of this possible metabolic susceptibility could deepen our knowledge of ALS pathomechanisms.File | Dimensione | Formato | |
---|---|---|---|
Verde F Neurol Sci 2019.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
289.55 kB
Formato
Adobe PDF
|
289.55 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.