title: Association of impulsivity and polymorphic microRNA-641 target sites in the SNAP-25 gene.
abstract: Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769) and two SNPs in the 3' UTR (rs3746544 and rs1051312) of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901) using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels.
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Németh
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Réka
authors.initials: R
authors.lastname: Kovács-Nagy
authors.affiliation: Institute of Psychology, Eotvos Lorand University, Budapest, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Székely
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Sasvári-Székely
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Rónai
mesh_terms: D000704:Analysis of Variance; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006814:Hungary; D007175:Impulsive Behavior / Q000235:genetics*; D008156:Luciferases; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics* / Q000378:metabolism; D001616:beta-Galactosidase
chemical_list: D017931:DNA Primers; C000591152:MIRN641 microRNA, human; D035683:MicroRNAs; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25; D008156:Luciferases; D001616:beta-Galactosidase