title: Novelty seeking mediates the effect of DRD3 variation on onset age of amphetamine dependence in Han Chinese population.
abstract: The dopamine receptor D3 (DRD3) gene, one of the candidate genes for amphetamine dependence (AD), is involved in the mesolimbic dopaminergic system, implicated as the underlying mechanism of addiction. Our case-control study aimed to investigate whether the DRD3 gene is associated with the susceptibility to AD and specific personality traits in AD patients. A total of 1060 unrelated Han Chinese subjects (559 AD patients and 501 controls) were screened using the same assessment tool and genotyped for eight DRD3 polymorphisms. All patients met the DSM-IV-TR criteria for AD, and personality traits of 539 were assessed using a Tridimensional Personality Questionnaire. Furthermore, AD individuals were divided into four clinical subgroups based on gender and psychosis status, to reduce the clinical heterogeneity. We found that the ATA haplotype combination for SNPs rs324029, rs6280, and rs9825563, respectively, was significantly associated with total AD patients (p = 0.0003 after 10,000 permutations). Similar results were observed in the both male and non-psychosis subgroup but not in other subgroups. In addition, DRD3 rs9825563 may influence onset age of drug use, partially mediated by novelty seeking in the non-psychosis AD group. In conclusion, DRD3 is a potential genetic factor in the susceptibility to AD and is associated with onset age of drug use through interaction with novelty seeking in a specific patient group in the Han Chinese population.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 144, Taiwan, ROC.
authors.forename: Shin-Chang
authors.initials: SC
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 144, Taiwan, ROC.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Yeh
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 144, Taiwan, ROC.
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Psychiatry, Taipei Branch, Buddhist Tzu Chi General Hospital, Taipei, Taiwan.
authors.forename: Chang-Chih
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 144, Taiwan, ROC.
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.|Division of Neurology, Department of Internal Medicine, Chiayi Yang-Ming Hospital, Chiayi, Taiwan, ROC.
authors.forename: Che-Hung
authors.initials: CH
authors.lastname: Yen
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chih-Sung
authors.initials: CS
authors.lastname: Liang
authors.affiliation: Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Pei-Shen
authors.initials: PS
authors.lastname: Ho
authors.affiliation: Institute of Behavior Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC. hsy@ndmctsgh.edu.tw.|Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 144, Taiwan, ROC. hsy@ndmctsgh.edu.tw.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
mesh_terms: D000328:Adult; D017668:Age of Onset; D019969:Amphetamine-Related Disorders / Q000235:genetics* / Q000523:psychology*; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D058999:Drug-Seeking Behavior; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010551:Personality; D010555:Personality Inventory; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012189:Retrospective Studies; D013624:Taiwan; D055815:Young Adult
chemical_list: C493593:DRD3 protein, human; D050637:Receptors, Dopamine D3
keywords: Amphetamine dependence; DRD3 gene; Onset age; Personality trait