Art, alpha-1-antitrypsin polymorphisms and intense creative energy : Blessing or curse?

摘要: Persons heterozygous for Z, S and rare alpha-1-antitrypsin (AAT, SERPIN1A) polymorphisms (ca. 9% of population) are often considered 'silent' carriers with increased vulnerability to environmentally modulated liver lung disease. They may have significantly more anxiety bipolar spectrum disorders, nutritional compromise, white matter disease [Schmechel DE, Browndyke J, Ghio A. Strategies the dissection genetic-environmental interactions in neurodegenerative disorders. Neurotoxicology 2006;27:637-57]. Given association art mood we examined occupation artistic vocation from this same series. One thousand five hundred thirty-seven consecutive persons aged 16-90 years old received comprehensive work-up including testing AAT 'phenotype' level, factors, inflammatory, iron copper indices. Occupations were grouped by Bureau Labor Standards classification information gathered on activities. Proportion reactive airway disease, obstructive pulmonary pre-existing disorder or carrying non-M compared normal MM genotype (respectively, 10, 20, 21, 33% 8, 12, 11, 9%; contingency table, pulmonary: chi2 37, p=0.0001; affective disorder: chi2=171, p=0.0001). In avocation (n=189) (n=57), proportions 44 40% background rate avocation: chi2=172, occupation: chi2=57, p=0.0007). Artistic ability 'anxiety/bipolar spectrum' disorders represent phenotypic attributes that had selective advantage during recent human evolution, an 'intensive creative energy' (ICE) behavioral phenotype. Background proportion ICE 7% consists 49 1312 (4%), 58 225 non-MM genotypes (26%) (contingency chi2=222, Penetrance increases lower levels: PiMS, 18%; PiMZ, 44%; PiSS PiZZ, 100% (five cases). At all ages, higher thiamine deficiency (50% PiMZ), hypoglycemia (20% possibly fatty (thiamine: chi2=28, hypoglycemia: chi2=92, older persons, PiMZ (46%) brain MRI T2 abnormalities (chi2=49, p=0.003). showed prevalence signature as Z homozygotes (see above). polymorphism was associated delayed age onset (average 7 years) toxic environmental occupational exposures (log rank, p=0.0001) stable cognitive change illness (p<0.05). phenotype altered homeostasis low absent non-ceruloplasmin bound which affect iron, lipid metabolism early events nervous system development, function response exposures. also be a 'switch' 'free' would theorized provide protection oxidation favorably beta-amyloid other aggregation, but alter 'critical' period CNS development. define important treatable subset presenting This new proposed transcends classic pattern strictly should proper evaluation management patients AAT-related ICE, multisystem memory.