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Y. WANG et al.

knock-out mice indicated that DAT1 may be involved in the development of ADHD [12,13]. These mice showed hyperactive behavior in the open field, and had difficulty in stopping












ADHD-like-behaviors were reduced by treatment of methylphenidate.

Over the past several years, there has been increasing interest in the potential involvement of DAT1 in ADHD. DAT1 is the second gene suspected to be related to ADHD in the field of molecular biology [14]. In 1995, as the pioneers, Cook and colleagues [15] first reported an association between ADHD and DAT1. They found that the 3’untranslated region (3’UTR) of DAT1 has a variable number of tandem repeat (VNTR) polymorphism and that ADHD was associated with a 10-repeat allele (480bp PCR fragment) of the VNTR. Subsequently, several research groups looked for an association between the DAT1 gene and ADHD [16-19]. Some of them used family-based association study method, some used case-control study method, and some used both methods, but the findings were inconsistent.

In China, two studies examined the association of DAT1 with ADHD in Chinese Han children and their findings were also contradictory. One of these studies [20] was conducted in Hong Kong and reported no relationship between DAT1 and ADHD. The other study [21], conducted in Beijing, found that long repeat alleles were associated with the disorder in a case-control analysis, but not family-based analysis, and stated that their positive finding should be interpreted cautiously.

As China has the largest population in the world, thus, further studies are needed to determine if there is a relationship between ADHD and DAT1. Specially, there is a need to replicate the molecular genetic linkage disequilibrium with ADHD in different area of China to establish a role of DAT1 in the etiology of ADHD. The main aim of the present study was to explore the possibility that DAT1 polymorphisms are in linkage disequilibrium with ADHD in Chinese children in Xi’an using a family-based association and case-control study designs.



The present study was approved by the Ethics Committee of Xi’an Jiaotong University. Written informed consent was obtained from the patients’ parents. The current study included 54 children with ADHD (9.4 ± 2.2 years), consisting of 42 boys and 12 girls, aged 6-16 years, and their biological parents, who visited the outpatient clinic of Child Development and Behavior Institute of the Second Affiliated Hospital, Xi’an Jiaotong University in Xi’an, PRC. Children were diagnosed as ADHD if they met DSM-IV criteria [1] for ADHD: six symptoms of inattention and/or hyperactivity-impulsivity either in the home or school setting determined by clinical interview, evidence of pervasiveness defined as a minimum of four symptoms in the non-criterion setting, and onset of symptoms before 7 years of age. Thirty-seven (68.5%) children met the criteria for the ADHD combined type (ADHD-C), 5 (9.3%) met the criteria for the ADHD hyperactive-impulsive type (ADHD-HI), and 12 (22.2%) met the criteria for the ADHD inattentive type (ADHD-I).

In addition to a family-based design, we included a control group to allow for a case-control design. The control group included 66 healthy individuals (8.6 ± 2.2 years), consisting of 46 boys and 20 girls, aged 6-14 years, who visited the hospital for health examinations, and were confirmed to have no evidence of medical or psychiatric illness.

All subjects involved in this study were Han Chinese. Interviews were conducted by at least two child psychiatrists (two of whom were Drs.Y.P.Wang and Z.H.Wang) with the clinical description of the patients’ parents and teachers. The intelligence quotient (IQ) of subjects was tested using the Chinese-Wechsler Intelligence Scale for Children (C-WISC),


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