title: Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder.
abstract: Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers on chromosome 12, D12S86 and D12S378, was the most probable genomic region to contain a susceptibility gene for affective disorders. Association studies with microsatellite markers using a case/control sample from the same population (n = 427) revealed significant allelic associations between the bipolar phenotype and marker NBG6. Since this marker is located in intron 9 of the P2RX7 gene, we analyzed the surrounding genomic region for the presence of polymorphisms in regulatory, coding and intron/exon junction sequences. Twenty four (24) SNPs were genotyped in a case/control sample and 12 SNPs in all pedigrees used for linkage analysis. Allelic, genotypic or family-based association studies suggest the presence of two susceptibility loci, the P2RX7 and CaMKK2 genes. The strongest association was observed in bipolar families at the non-synonymous SNP P2RX7-E13A (rs2230912, P-value = 0.000708), which results from an over-transmission of the mutant G-allele to affected offspring. This Gln460Arg polymorphism occurs at an amino acid that is conserved between humans and rodents and is located in the C-terminal domain of the P2X7 receptor, known to be essential for normal P2RX7 function.
authors: Neuroscience, CHUL Research Centre and Université Laval, Quebec, Canada. barden@crchul.ulaval.ca
authors: Nicholas
authors: N
authors: Barden
authors: Mario
authors: M
authors: Harvey
authors: Bernard
authors: B
authors: Gagné
authors: Eric
authors: E
authors: Shink
authors: Monique
authors: M
authors: Tremblay
authors: Catherine
authors: C
authors: Raymond
authors: Michel
authors: M
authors: Labbé
authors: André
authors: A
authors: Villeneuve
authors: Denis
authors: D
authors: Rochette
authors: Lise
authors: L
authors: Bordeleau
authors: Herbert
authors: H
authors: Stadler
authors: Florian
authors: F
authors: Holsboer
authors: Bertram
authors: B
authors: Müller-Myhsok