title: Genetic background predicts poor prognosis in frontotemporal lobar degeneration.
abstract: BACKGROUND
  Ruling out predictors of survival in frontotemporal lobar degeneration (FTLD) is a clinical challenge for defining disease outcomes and monitoring therapeutic interventions. Little is known about determinants of survival in FTLD.
  
  
  OBJECTIVE
  The aim of the present study was to identify whether genetic determinants are key, not only as risk factors but as predictors of survival in FTLD.
  
  
  METHODS
  Ninety-seven FTLD patients were considered in the present study. A clinical evaluation and a standardized assessment were carried out. Each patient underwent blood sampling for genetic testing, and mutations within the progranulin (PGRN) gene, microtubule-associated protein tau (MAPT) haplotype, apolipoprotein E (APOE) genotype and 4 vascular endothelial growth factor (VEGF) polymorphisms were evaluated. Discrete-time survival models were applied.
  
  
  RESULTS
  Monogenic FTLD due to PGRN mutations [odds ratio (OR) = 3.62, 95% confidence interval (CI) = 1.12-11.7; p = 0.032], and MAPT *H2 haplotype (OR = 3.23, 95% CI = 1.08-9.69; p = 0.036) were associated with an increased hazard risk of poor outcome. Conversely, APOE genotype, and VEGF polymorphisms were not associated with survival risk in the FTLD sample.
  
  
  CONCLUSIONS
  Genetic background is not only crucial in disease pathogenesis, but it also modulates disease course. Genetic factors influencing prognosis should be taken into account to include homogeneous groups in future clinical trials and to monitor efficacy of future interventions.
authors.affiliation: Center for Aging Brain and Dementia, Department of Neurology, University of Brescia, Brescia, Italy. bborroni @ inwind.it
authors.forename: B
authors.initials: B
authors.lastname: Borroni
authors.forename: M
authors.initials: M
authors.lastname: Grassi
authors.forename: S
authors.initials: S
authors.lastname: Archetti
authors.forename: A
authors.initials: A
authors.lastname: Papetti
authors.forename: R
authors.initials: R
authors.lastname: Del Bo
authors.forename: C
authors.initials: C
authors.lastname: Bonvicini
authors.forename: G P
authors.initials: GP
authors.lastname: Comi
authors.forename: M
authors.initials: M
authors.lastname: Gennarelli
authors.forename: G
authors.initials: G
authors.lastname: Bellelli
authors.forename: M
authors.initials: M
authors.lastname: Di Luca
authors.forename: A
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate / Q000639:trends; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D005819:Genetic Markers; C054369:MAPT protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016875:tau Proteins