Genetic and nongenetic factors associated with CADASIL: a retrospective cohort study

ABSTRACT: Objective: To examine the relationships between genetic variables (genotype–phenotype) and cardiovascular risk factors in the natural history of CADASIL. Methods: This was a retrospective cohort study of 331 individuals, 90 were carriers of four mutations in the NOTCH3 gene. Cox proportional hazards models were fitted to estimate the effect of genetic and cardiovascular factors on the onset of migraine, first stroke, and dementia. Competing risk regression models considered death as risk. Results: Noncarriers and NOTCH3 mutation carriers had similar frequencies for all cardiovascular risk factors. Diabetes (SHR 3.5, 95% CI 1.75–7.15) was associated with a younger age at onset of strokes among carriers. Additionally, a genotype–phenotype relationship was observed among C455R mutation carriers, with higher frequency of migraines (100%), younger age at onset of migraine (median age 7 years, IQR 8) and cerebrovascular events (median age 30.5 years, IQR 26). Moreover, fewer carriers of the R141C mutation exhibited migraines (20%), and it was even lower than the frequency observed in the noncarrier group (44.8%). Conclusions: This study characterizes extended family groups, allowing us a comparison in the genotype–phenotype. The results suggest a complex interplay of genetic and cardiovascular risk factors that may help explain the variability in the clinical presentation and severity of CADASIL

• Autores: Ospina Villegas, Carolina; Aguirre Acevedo, Daniel Camilo; Lopera Restrepo, Francisco J; Arboleda Velasquez, Joseph F; Quiroz, Yakeel; Castaño-Zuluaga, Yessica; Velilla, Lina; García Ospina, Gloria
• Tipo de recurso: Tesis
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng; spa
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/16669
• Acceso en línea: http://hdl.handle.net/10495/16669
• Palabra clave: CADASIL; Genotipo; Genotype; Fenotipo; Phenotype; Tabaquismo; Tobacco Use Disorder; Demencia; Dementia; Accidente Cerebrovascular; Stroke; Trastornos Migrañosos; Migraine Disorders
• Rights: embargoedAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/