title: Association of a new polymorphism in ALOX12 gene with bipolar disorder.
abstract: Bipolar disorder (BPD) is characterised by episodes of excitement interspersed with periods of depression. The role of genetic factors in BPD is indicated by studies in monozygotic twins showing 40-70 % of concordance. Studies using genetic markers showed linkage of genes for affective disorders in different chromosome regions, emphasising the polygenic and multifactorial traits. The main goal of our research is to search non-synonymous SNPs (those that result in modifications in protein sequence) in genes that can be associated with psychiatric diseases as suggested by genomic mapping and/or by physiological function of the protein. Using DNA sequencing we could confirm a new non-synonymous SNP in the conservative domain of the ALOX12 gene (17p13.1), suggested by EST alignment. This SNP is an alteration from G to A that leads to a change of an arginine (A) to a glutamine in one of the most important domains of the protein. This SNP was evaluated by DNA sequencing in 182 patients with BPD and 160 control individuals. An increased presence of allele A among patients (60 % in controls and 73.1 % in cases; chi(2) = 6.581, P = 0.010; OR = 1.8095, 95 % CI = 1.1477-2.853) was found, suggesting an association of this polymorphism with the BPD in this Brazilian sample.
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. cintiafri@hotmail.com
authors.forename: Cintia
authors.initials: C
authors.lastname: Fridman
authors.forename: Elida P B
authors.initials: EP
authors.lastname: Ojopi
authors.forename: Sheila P
authors.initials: SP
authors.lastname: Gregório
authors.forename: Elisa H
authors.initials: EH
authors.lastname: Ikenaga
authors.forename: Doris H
authors.initials: DH
authors.lastname: Moreno
authors.forename: Frederico N
authors.initials: FN
authors.lastname: Demetrio
authors.forename: Pedro E M
authors.initials: PE
authors.lastname: Guimarães
authors.forename: Homero P
authors.initials: HP
authors.lastname: Vallada
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dias Neto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics* / Q000628:therapy; D001938:Brazil; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D006801:Humans; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
chemical_list: D008094:Lithium; D001092:Arachidonate 12-Lipoxygenase; C476558:ALOX12 protein, human