title: Investigating SAPAP3 variants in the etiology of obsessive-compulsive disorder and trichotillomania in the South African white population.
abstract: BACKGROUND
  Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by repeated obsessions and compulsions. Trichotillomania (TTM), a psychiatric disorder characterized by repetitive hairpulling, is presently classified as an impulse control disorder, but has also been viewed as an obsessive-compulsive spectrum disorder. Both conditions are complex disorders, with evidence from family and twin studies indicating that their etiology includes a genetic component. Results from a recent knockout animal model suggest that SAP90/PSD95-associated protein 3 (SAPAP3) may be involved in the pathophysiology of both disorders.
  
  
  METHODS
  Seven polymorphic variants distributed across the gene encoding SAPAP3 were genotyped in South African white OCD (n = 172), TTM (n = 45), and control (n = 153) subjects. Single-locus and haplotype analyses were conducted to determine association between genetic variants and subjects with OCD, TTM, and controls.
  
  
  RESULTS
  Although single-locus analysis revealed a significant association between rs11583978 in SAPAP3 and TTM, this association was nonsignificant after correction for multiple testing. In the OCD group, a significant association was observed between earlier age at onset and the A-T-A-T (rs11583978-rs7541937-rs6662980-rs4652867) haplotype compared with the C-G-G-G haplotype.
  
  
  CONCLUSIONS
  This study generated preliminary evidence to link SAPAP3 variants to the development of earlier onset OCD. Future studies should concentrate on locating the susceptibility variant(s) by focusing on functional polymorphisms within SAPAP3.
authors.affiliation: Division of Molecular Biology and Human Genetics, Department Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa. smjh@sun.ac.za
authors.forename: Leigh
authors.initials: L
authors.lastname: Boardman
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Christine
authors.initials: C
authors.lastname: Lochner
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Kinnear
authors.forename: Soraya
authors.initials: S
authors.lastname: Seedat
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Moolman-Smook
authors.forename: Sian M J
authors.initials: SM
authors.lastname: Hemmings
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D013019:South Africa / Q000208:ethnology; D014256:Trichotillomania / Q000175:diagnosis / Q000235:genetics*; D044465:White People / Q000235:genetics / Q000523:psychology
chemical_list: C543515:DLGAP3 protein, human; D009419:Nerve Tissue Proteins