title: Nucleotide sequence variation within the PI3K p85 alpha gene associates with alcohol risk drinking behaviour in adolescents.
abstract: BACKGROUND
  While the phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is typically known to regulate cell growth and survival, emerging evidence suggest a role for this pathway in regulating the behavioural responses to addictive drugs.
  
  
  RESULTS
  To investigate whether PI3K contributes to patterns of risky alcohol drinking in human, we investigated genetic variations in PIK3R1, encoding the 85 kD regulatory subunit of PIK, in 145 family trios consisting of 15-16 year old adolescents and their parents. Screening for mutations in exons, exon-intron boundaries and regulatory sequences, we identified 14 single nucleotide polymorphisms (SNPs) in the PIK3R1 gene region from exon 1 to the beginning of the 3' untranslated region (UTR). These SNPs defined haplotypes for the respective PIK3R1 region. Four haplotype tagging (ht)SNPs (rs706713, rs2302975, rs171649 and rs1043526), discriminating all haplotypes with a frequency >or=4.5% were identified. These htSNPs were used to genotype adolescents from the "Mannheim Study of Risk Children" (MARC). Transmission disequilibrium tests in these adolescents and their parents demonstrated sex-specific association of two SNPs, rs2302975 and rs1043526, with patterns of risky alcohol consumption in male adolescents, including lifetime prevalence of drunkenness (p = 0.0019 and 0.0379, respectively) and elevated maximum amount of drinking (p = 0.0020 and 0.0494, respectively), as a measure for binge drinking pattern.
  
  
  CONCLUSIONS
  Our findings highlight a previously unknown relevance of PIK3R1 genotypes for alcohol use disorders and might help discriminate individuals at risk for alcoholism.
authors.affiliation: Section of Addiction Biology, Interdisciplinary Research Group Addiction and NIHR-Biomedical Research Centre, Institute of Psychiatry, King's College, London, United Kingdom.
authors.forename: Sylvane
authors.initials: S
authors.lastname: Desrivières
authors.forename: Kristina
authors.initials: K
authors.lastname: Krause
authors.forename: Anne
authors.initials: A
authors.lastname: Dyer
authors.forename: Josef
authors.initials: J
authors.lastname: Frank
authors.forename: Dorothea
authors.initials: D
authors.lastname: Blomeyer
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Manfred
authors.initials: M
authors.lastname: Laucht
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior; D000428:Alcohol Drinking / Q000235:genetics*; D000483:Alleles; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D019869:Phosphatidylinositol 3-Kinases