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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Paraoxonase gene polymorphisms and sporadic ALS
A Slowik1, B Tomik, P P Wolkow
1Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland. slowik@cm-uj.krakow.pl
Neurology
|July 11, 2006
Summary
Genetic variants in paraoxonase 1 and 2 genes are linked to sporadic ALS risk. Specific PON1 and PON2 polymorphisms, including the R-C haplotype, were significantly associated with sporadic ALS in a Polish population.
Area of Science:
- Genetics
- Neuroscience
- Biochemistry
Background:
- The human paraoxonase (PON) gene family, comprising PON1, PON2, and PON3, is located on chromosome 7.
- PON gene variants may influence enzyme activity.
- Environmental factors and chemical exposures metabolized by paraoxonases could be risk factors for sporadic ALS (sALS).
Purpose of the Study:
- To investigate the association between functional polymorphisms in PON1 (Q192R, L55M) and PON2 (C311S) and the risk of developing sALS.
- The study focused on a Polish population.
Main Methods:
- Case-control study design involving 185 sALS patients and 437 healthy controls.
- Genotyping of paraoxonase polymorphisms was performed using Polymerase Chain Reaction (PCR) and restriction enzyme digestion.
- Logistic regression and haplotype analyses were employed to assess associations.
Main Results:
- The C allele of the PON2 C311S polymorphism showed association with sALS in dominant and additive models.
- The R allele of the PON1 Q192R polymorphism was associated with sALS in recessive, additive, and dominant models.
- The R-C haplotype was significantly overrepresented in sALS cases compared to controls (OR=3.44, p=0.002).
Conclusions:
- Specific amino acid variants in PON1 and PON2 genes are associated with an increased risk of sporadic ALS.
- These findings highlight the potential role of paraoxonase gene polymorphisms in sALS pathogenesis within the studied population.
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