The CST3 B haplotype is associated with frontotemporal lobar degeneration.
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.
Benussi
L
L
NeuroBioGen Lab-Memory Clinic, IRCCS "S. Giovanni di Dio-FBF", Brescia, Italy.
Ghidoni
R
R
Galimberti
D
D
Boccardi
M
M
Fenoglio
C
C
Scarpini
E
E
Frisoni
G B
GB
Binetti
G
G
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
C525030:CST3 protein, human; D055316:Cystatin C; C492314:GRN protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins