title: The CST3 B haplotype is associated with frontotemporal lobar degeneration.
abstract: OBJECTIVE
  Frontotemporal lobar degeneration (FTLD) is a common cause of early-onset dementia. Given the role of cystatin C in brain neurodegeneration and neuroregeneration, the aim of this study was to determine whether the cystatin C gene (CST3) was genetically associated with FTLD.
  
  
  METHODS
  Hundred and eighty-six FTLD patients and 457 controls underwent CST3 analysis by PCR and KspI enzyme digestion.
  
  
  RESULTS
  In FTLD patients negative for the presence of PGRN mutations, we found an over-representation of the CST3 haplotype B [odds ratio (OR = 1.619, P = 0.002)] and of AB/BB genotypes (OR = 1.704, P = 0.008) in FTLD patients.
  
  
  CONCLUSIONS
  The present study indicated the CST3 B haplotype as a putative risk factor for FTLD in PGRN mutations negative patients. The reduced level of cystatin C, previously associated with the B haplotype, might represent the molecular factor responsible for the increased risk. Long-term depletion of neurotrophic factors, such as cystatin C and progranulin proteins, seem to be a common theme in FTLD: boosting the expression of such proteins might be a promising therapeutic strategy for FTLD.
authors: NeuroBioGen Lab-Memory Clinic, IRCCS "S. Giovanni di Dio-FBF", Brescia, Italy.
authors: L
authors: L
authors: Benussi
authors: R
authors: R
authors: Ghidoni
authors: D
authors: D
authors: Galimberti
authors: M
authors: M
authors: Boccardi
authors: C
authors: C
authors: Fenoglio
authors: E
authors: E
authors: Scarpini
authors: G B
authors: GB
authors: Frisoni
authors: G
authors: G
authors: Binetti
mesh_terms: D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D055316:Cystatin C / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000077153:Progranulins; D012307:Risk Factors
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; C492314:GRN protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins