Paraoxonase gene polymorphisms and sporadic ALS

Słowik, Agnieszka; Tomik, Barbara; Wołkow, Paweł; Partyka, Dorota; Turaj, Wojciech; Małecki, Maciej; Pera, Joanna; Dziedzic, Tomasz; Szczudlik, Andrzej; Figlewicz, D. A.

doi:10.1212/01.wnl.0000219565.32247.11

Cited by 82 publications

(55 citation statements)

References 30 publications

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“…Interestingly, recent studies have established that different functional PON polymorphisms are risk factors for different neurological diseases [22, 23]. It is possible that enhanced lipid peroxides target specific cells in different populations of patients; i.e.…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

et al. 2007

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Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

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Section: Discussionmentioning

confidence: 99%

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

et al. 2007

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“…The cause of sporadic ALS is thought to be multifactorial, with environmental, infectious and genetic etiologies. Reported associations with variants in diverse genes (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) have proven difficult to replicate. Advances in the technology for large-scale genotyping of single nucleotide polymorphisms (SNPs) have facilitated unbiased, genome-wide association studies.…”

mentioning

confidence: 99%

Reduced expression of the Kinesin-Associated Protein 3 ( KIFAP3 ) gene increases survival in sporadic amyotrophic lateral sclerosis

Landers

Melki

Meininger

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

168

110

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Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and is uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility and phenotypes in sporadic ALS, we performed a genome-wide SNP analysis in sporadic ALS cases and controls. A total of 288,357 SNPs were screened in a set of 1,821 sporadic ALS cases and 2,258 controls from the U.S. and Europe. Survival analysis was performed using 1,014 deceased sporadic cases. Top results for susceptibility were further screened in an independent sample set of 538 ALS cases and 556 controls. SNP rs1541160 within the KIFAP3 gene (encoding a kinesin-associated protein) yielded a genomewide significant result (P ‫؍‬ 1.84 ؋ 10 ؊8 ) that withstood Bonferroni correction for association with survival. Homozygosity for the favorable allele (CC) conferred a 14.0 months survival advantage. Sequence, genotypic and functional analyses revealed that there is linkage disequilibrium between rs1541160 and SNP rs522444 within the KIFAP3 promoter and that the favorable alleles of rs1541160 and rs522444 correlate with reduced KIFAP3 expression. No SNPs were associated with risk of sporadic ALS, site of onset, or age of onset. We have identified a variant within the KIFAP3 gene that is associated with decreased KIFAP3 expression and increased survival in sporadic ALS. These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability.genome-wide association study ͉ single nucleotide polymorphism A myotrophic lateral sclerosis (ALS) is an age-dependent, degenerative disorder of motor neurons (1) that typically develops in the 6th decade and is uniformly fatal, usually within 5 years (2). Approximately 10% of ALS cases are dominantly inherited (3); 20% of these are caused by mutations in the gene encoding copper/zinc superoxide dismutase 1 (SOD1) (4); mutations in the TARDBP gene (5, 6) account for Ϸ5% of cases. Rare familial cases arise from mutations in genes encoding the vesicle-associated membrane associated protein B (7), alsin (a RAB5-guanine nucleotide exchange factor) (8, 9), senataxin (10) or dynactin (11). Recently, we reported that Ϸ5% of familial ALS cases are due to mutations in the FUS/TLS gene (12, 13) whose product binds DNA and RNA, as does TARDBP. The cause of sporadic ALS is thought to be multifactorial, with environmental, infectious and genetic etiologies. Reported associations with variants in diverse genes (14-25) have proven difficult to replicate. Advances in the technology for large-scale genotyping of single nucleotide polymorphisms (SNPs) have facilitated unbiased, genome-wide association studies. Examples include the identification of IL2RA and IL7RA variants as risk factors for multiple sclerosis (26-28) and the recent reports of 6 new gene regions associated with type 2 diabetes (29)(30)(31)(32)(33)(34)(35). To test the hypothesis that commonly occurring genetic

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“…Because PON proteins reduce oxidation and are able to detoxify neurotoxins these proteins have been investigated for association with ALS. Polymorphisms in PON1 and PON2 as well as a haploblock spanning PON2 and PON3 were found to be associated with sALS (Saeed et al, 2006;Slowik et al, 2006). Since then several other studies in different populations have reported association of SNPs in the PON genes with sALS Landers et al, 2008;Morahan et al, 2007;.…”

Section: Paraoxonase Genes (Pon)mentioning

confidence: 96%

Genetics of Amyotrophic Lateral Sclerosis

Devil

Andersen

Bosch

et al. 2012

Amyotrophic Lateral Sclerosis

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Paraoxonase gene polymorphisms and sporadic ALS

Abstract: Frequent amino acid variants in the paraoxonase 1 and paraoxonase 2 genes are associated with sporadic ALS in a Polish population.

Cited by 82 publications

References 30 publications

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

Reduced expression of the Kinesin-Associated Protein 3 ( KIFAP3 ) gene increases survival in sporadic amyotrophic lateral sclerosis

Genetics of Amyotrophic Lateral Sclerosis

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