title: Variation in PPP3CC Genotype Is Associated with Long-Term Recovery after Severe Brain Injury.
abstract: After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). The following tagging single nucleotide polymorphisms (tSNPs) in PPP3CC were genotyped: rs2443504, rs2461491, rs2469749, and rs10108011. The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.
authors.affiliation: 1 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.|3 School of Nursing, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Osier
authors.affiliation: 2 Department of Neurosurgery, University of Washington , Seattle, Washington.
authors.forename: James W
authors.initials: JW
authors.lastname: Bales
authors.affiliation: 1 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.|4 Safar Center for Resuscitation Research, Seton Hill University , Greensburg, Pennsylvania.
authors.forename: Bunny
authors.initials: B
authors.lastname: Pugh
authors.affiliation: 1 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Samuel
authors.initials: S
authors.lastname: Shin
authors.affiliation: 5 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Julie
authors.initials: J
authors.lastname: Wyrobek
authors.affiliation: 6 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.affiliation: 6 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.affiliation: 3 School of Nursing, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Dianxu
authors.initials: D
authors.lastname: Ren
authors.affiliation: 3 School of Nursing, University of Pittsburgh , Pittsburgh, Pennsylvania.|7 School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Sheila
authors.initials: S
authors.lastname: Alexander
authors.affiliation: 3 School of Nursing, University of Pittsburgh , Pittsburgh, Pennsylvania.|8 Department of Human Genetics, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.affiliation: 1 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.|6 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.|9 VA Pittsburgh Healthcare System , Pittsburgh, Pennsylvania.
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D019703:Calcineurin / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D023261:Glasgow Outcome Scale / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020127:Recovery of Function / Q000235:genetics*; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D019703:Calcineurin; C525675:PPP3CC protein, human
keywords: cognitive function; outcome measures; recovery; traumatic brain injury