title: Association analysis of dopaminergic gene variants (Comt, Drd4 And Dat1) with Alzheimer s disease.
abstract: Defects in dopaminergic transmission play important roles in the disturbance of synaptic plasticity and even in advanced cognitive behavior. However, the relationship between genes involved in the regulation of dopamine levels and predisposition for Alzheimer s disease (AD) remains unclear. The potential association of dopamine-modulating gene polymorphisms with AD was evaluated. We performed a case-control study with 120 patients and 86 healthy controls. Two catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms (SNPs) (rs2020917 and rs4646312), two dopamine D4 receptor (DRD4) SNPs (rs3758653 and rs916455), and four dopamine transporter (DAT1) SNPs (rs2937639, rs6347, rs12516948 and rs11133762) were investigated. The T allele at the DRD4 SNP (rs3758653) was found to be significantly associated with AD. Our results also showed that haplotype frequencies, observed from the analyzed SNPs, were distributed significantly differently in AD patients vs control subjects. Moreover, a strong association was observed between the A allele at rs6347 of DAT1 and moderate stage of dementia. These observations suggest that genetic variations in the dopamine-modulating genes, COMT, DRD4 and DAT1, may contribute to AD pathogenesis in the Taiwanese population.
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: W Y
authors.initials: WY
authors.lastname: Lin
authors.forename: B T
authors.initials: BT
authors.lastname: Wu
authors.forename: C C
authors.initials: CC
authors.lastname: Lee
authors.forename: J J
authors.initials: JJ
authors.lastname: Sheu
authors.forename: S H
authors.initials: SH
authors.lastname: Liu
authors.forename: W F
authors.initials: WF
authors.lastname: Wang
authors.forename: C H
authors.initials: CH
authors.lastname: Tsai
authors.forename: H P
authors.initials: HP
authors.lastname: Liu
authors.forename: F J
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050638:Receptors, Dopamine D4 / Q000235:genetics* / Q000378:metabolism; D013624:Taiwan
chemical_list: C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D002394:Catechol O-Methyltransferase