Mensch, Welt, Widerspruch : Bamberger Hegelwochen 96

Mensch, Welt, Widerspruch : Bamberger Hegelwochen 199

Population stratification may bias analysis of PGC-1α as a modifier of age at Huntington disease motor onset

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive and behavioral disturbances, caused by the expansion of a CAG trinucleotide repeat in the HD gene. The CAG allele size is the major determinant of age at onset (AO) of motor symptoms, although the remaining variance in AO is highly heritable. The rs7665116 SNP in PPARGC1A, encoding the mitochondrial regulator PGC-1α, has been reported to be a significant modifier of AO in three European HD cohorts, perhaps due to affected cases from Italy. We attempted to replicate these findings in a large collection of (1,727) HD patient DNA samples of European origin. In the entire cohort, rs7665116 showed a significant effect in the dominant model (p value = 0.008) and the additive model (p value = 0.009). However, when examined by origin, cases of Southern European origin had an increased rs7665116 minor allele frequency (MAF), consistent with this being an ancestry-tagging SNP. The Southern European cases, despite similar mean CAG allele size, had a significantly older mean AO (p < 0.001), suggesting population-dependent phenotype stratification. When the generalized estimating equations models were adjusted for ancestry, the effect of the rs7665116 genotype on AO decreased dramatically. Our results do not support rs7665116 as a modifier of AO of motor symptoms, as we found evidence for a dramatic effect of phenotypic (AO) and genotypic (MAF) stratification among European cohorts that was not considered in previously reported association studies. A significantly older AO in Southern Europe may reflect population differences in genetic or environmental factors that warrant further investigation

Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington’s disease motor onset

Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis. We used genetic association analysis in 1,628 HD patients to evaluate candidate polymorphisms in N-methyl-D-aspartate receptor subtype genes (GRIN2A rs4998386 and rs2650427, and GRIN2B rs1806201) and functional polymorphisms in genes in the dopamine pathway (DAT1 3′ UTR 40-bp variable number tandem repeat (VNTR), DRD4 exon 3 48-bp VNTR, DRD2 rs1800497, and COMT rs4608) as potential modifiers of the disease process. None of the seven polymorphisms tested was found to be associated with significant modification of motor AO, either in a dominant or additive model, after adjusting for ancestry. The results of this candidate-genetic study therefore do not provide strong evidence to support a modulatory role for these variations within glutamatergic and dopaminergic genes in the AO of HD motor manifestations

De l'administration du savoir

L'administration du savoir est à la fois indispensable à la recherche et contraire, par nature, paradoxalement, à certains de ses besoins essentiels. Elle tend, par souci de justice et de simplicité, à considérer le champ de la recherche comme plus homogène qu'il ne l'est, à le simplifier et le rigidifier, et à sous-estimer le risque, le tâtonnement, la mobilité des hypothèses.Hersch Jeanne. De l'administration du savoir. In: Politiques et management public, vol. 12, n° 2, 1994. Administrer les savoirs : leur production, leur transmission, leur application, leur contrôle - Actes du Sixième Colloque International, Genève - 25/26 mars 1993. pp. 17-24

S'adapter et résister

Lorsque j'ai proposé le titre de cet exposé : S'adapter et résister, j'ignorais que Manès Sperber avait prononcé un discours intitulé : Dialectique de l'adaptation et de la résistance, en 1980, à l'université de Munich, à la mémoire des frère et sœur Scholl, exécutés le 22 février 1943, avec leurs camarades, pour avoir diffusé par tract des informations vraies. J'avais donc choisi ce thème, sans le savoir, simplement parce qu'il me semblait permettre de viser dans la vie, dans l'œuvre et même..