title: Progranulin gene variability and plasma levels in bipolar disorder and schizophrenia.
abstract: Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n = 271) or BPD (n = 237) as compared with 574 age-, gender- and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls.A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR:0.63, 95%CI:0.49-0.80), rs4792938 (30.7 versus 39.7%, P = 0.005, OR: 0.70, 95%CI: 0.55-0.89) and rs5848 (30.3 versus 36.8, P = 0.007, OR: 0.71, 95%CI: 0.56-0.91). Mean±SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69±3.97 and 116.14±5.80 ng/ml, respectively, versus 180.81±18.39 ng/ml P<0.001) and were not correlated with age.In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.
authors.affiliation: Department of Neurological Sciences, University of Milan, IRCCS Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy. daniela.galimberti@unimi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dell'Osso
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
authors.forename: Johannes
authors.initials: J
authors.lastname: Weigl
authors.forename: Maria
authors.initials: M
authors.lastname: Neuner
authors.forename: Juliane
authors.initials: J
authors.lastname: Volkert
authors.forename: C
authors.initials: C
authors.lastname: Leonhard
authors.forename: David G
authors.initials: DG
authors.lastname: Olmes
authors.forename: Juliane
authors.initials: J
authors.lastname: Kopf
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Ridolfi
authors.forename: Carlotta
authors.initials: C
authors.lastname: Palazzo
authors.forename: Laura
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: A C
authors.initials: AC
authors.lastname: Altamura
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001714:Bipolar Disorder / Q000097:blood* / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000097:blood / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077153:Progranulins; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins