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Sökning: WFRF:(Kamel Freya)

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1.
  • Mariosa, Daniela, et al. (författare)
  • Antidiabetics, Statins, and the Risk of Amyotrophic Lateral Sclerosis
  • 2020
  • Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 27:6, s. 1010-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Medications that are used for treatment of metabolic disorders have been suggested to be associated with the development of amyotrophic lateral sclerosis (ALS).METHODS: To examine the associations of antidiabetics and statins with the subsequent risk of ALS we conducted a population-based nested case-control study of 2,475 Swedish residents diagnosed with ALS during July 2006-December 2013, and 12,375 population controls (five for each ALS case). We extracted from the Swedish Prescribed Drug Register information on filled prescriptions of antidiabetics and statins for both cases and controls during the years before ALS diagnosis. Conditional logistic regression was used to calculate odds ratios (ORs) for the associations of these medications with ALS risk.RESULTS: ALS patients were less likely to have been prescribed with antidiabetics, compared to controls (OR=0.76, 95%CI=0.65-0.90). Conversely, statins were not associated with ALS risk overall (OR=1.08, 95%CI=0.98-1.19), although a positive association was noted among women (OR=1.28, 95%CI=1.10-1.48). The latter association was mostly explained by ALS cases being more likely to have a first prescription of statins during the year before diagnosis, compared to controls (OR=2.54, 95%CI=1.84-3.49).CONCLUSIONS: The inverse association of antidiabetics with ALS is consistent with the previously reported inverse association between type 2 diabetes and ALS risk. The increase in prescription of statins during the year before ALS diagnosis deserves attention because it might reflect an acceleration of the course of ALS due to statin use.
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2.
  • Nicolas, Aude, et al. (författare)
  • Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
  • 2018
  • Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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