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structural differences in human DAT protein. VNTR may function as transcriptional regulators [27]. In this study, we investigated the relationship of ADHD and the DAT1 gene polymorphism through family-based and case-control association studies, focusing on variation in the 3’untranslated region. Consistent with previous findings, we didn’t find an association for the Chinese Han samples. This was true for both case-control and family-based analyses.

Cook et al. [15] originally reported that the 10-repeat allele of VNTR was associated with ADHD. Attempts to replicate these results were made in different populations [22,28,29]. However, in Asia, two Korean and two Chinese studies denied the association, especially using TDT [16,18,20,21]. The diverse ethnic backgrounds of individuals in the population and the clinical heterogeneity of ADHD itself may account for non-replications of earlier findings to some extent. The 10 repeat allele of the DAT1 gene polymorphism is significantly higher in populations in Mongolian, Japanese and Chinese than in Europeans [30,31]. In the present study, the high frequency of the 10-repeat allele of DAT1 and extremely low frequency of the 7-repeat allele of DAT1 are consistent with previous findings in the Chinese population [30,31], which supports the conclusion that there was no significant sampling bias in this study population.

The cause of ADHD is thought to involve a complex mix of multiple genes and multiple specific environmental risks [32,33]. The past decade of research has revealed just how difficult it is to find genes that contribute to variance in complex traits.

Based upon these data, there are some limitations to our study. Our sample size is not large enough to detect a weak association; large numbers of subjects in different races of Chinese from different areas should be further studied. Furthermore, though we analyzed only one gene in our research, to the best of our knowledge, for complex disorders, gene-gene interactions and gene-environment interactions should be considered in future studies in same sample at once time. Analyses of different genes involved in the etiology of ADHD enhance our understanding on the genetic contributions to the etiology of ADHD, but not understanding on the role of DAT1 itself. To enhance our understanding on the role of DAT1, we need to perform more biological studies on the effects of different polymorphisms on the gene and protein functions, and to study other genetic and environmental modifiers of the DAT1 gene. Apart from sample size, clinical homogeneity of subjects is also crucial for genetic association study of complex disease. This should be addressed. Further studies should employ a more homogenous sample, e.g., same diagnostic subtype or same phenotype as defined by psychometric tests.

In summary, our results do not support the possibility that DAT1 gene 3’VNTR polymorphism contributes to ADHD, although further studies are needed to confirm this in different populations in different environments.


We thank the patients and family members who participated in this study, as well as the teachers. We also extend our appreciation to Dr. Jianghua Lai and Ms. Junhai Zhao for their technical advices. This research was supported by Shaanxi Province Nature Science Foundation (No. 99sm57) and the Public Health Bureau of Shaanxi Province (No. 9931).



American Psychiatric Association. 1994. Diagnostic and statistic manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DC.


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