No association between VNTR polymorphisms of dopamine transporter gene and attention deficit hyperactivity disorder in Chinese children

Abstract

Dopamine transporter (DAT) gene is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Previously a meta-analysis concluded no association between the variable-number-of-tandem-repeats (VNTR) polymorphisms of the DAT gene and ADHD. However, significant heterogeneity was present among studies and no conclusion can be drawn about the association in any single ethnicity given the small number of studies. There were also conflicting results in Chinese populations. We therefore perform the present study to investigate the association in Chinese children in Hong Kong. In this prospective family-based and case-control study during January to June 2004, we recruited consecutive Chinese children diagnosed with ADHD by DSM-IV criteria, their family members, and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, mental retardation, or neurological deficits. VNTR polymorphisms of the DAT gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four ADHD cases (52 boys, 12 girls), their family members and 64 normal controls were recruited. The 10-repeat allele (92.6%) and the 10/10 repeat genotype (85.2%) were the most prevalent. Both family-based and case-control analyses showed no association between the DAT gene polymorphisms and ADHD (transmission dysequilibrium test: P = 0.99; odds ratio of 10-repeat allele = 0.89 (95%CI 0.35-2.28), P = 0.81; odds ratio of 10/10 repeat genotype = 0.69 (95%CI 0.26-1.84), P = 0.46). We concluded that VNTR polymorphism of the DAT gene is not associated with ADHD in Chinese children, and further studies are needed to clarify the polygenic and environmental influences for pathogenesis of ADHD.

Candidate gene studies of ADHD: a meta-analytic review

“…For the 3ЈUTR VNTR, independent data were available from 15 TDT Brookes et al 2006b;Curran et al 2001b;Feng et al 2005b;Galili-Weisstub and Segman 2003;Hebebrand et al 2006;Kim et al 2005b;Kustanovich et al 2004;Lim et al 2006;Maher et al 2002;Mick et al unpublished data;Todd et al 2001a;Waldman et al 1998) and 19 Case-Control/HHRR studies (Bakker et al 2005;Banoei et al 2008;Bobb et al 2005;Carrasco et al 2004;Cheuk et al 2006b;Cook et al 1995;Cornish et al 2005;Das and Mukhopadhyay 2007;Genro et al 2007;Hawi et al 2003;Jiang et al 1999;Kim et al 2006b;Kopeckova et al 2008;Langley et al 2005;Qian et al 2004;Simsek et al 2005;Smith et al 2003;Swanson et al 2000b;Wang et al 2008), with the 480-bp (or 10-repeat) allele designated as the "risk" allele. Results of this meta-analysis, shown in Fig.…”

Molecular Genetics of Monoamine Transporters: Relevance to Brain Disorders

“…For example, a recent study has demonstrated an association of the 9/10 genotype with more severe symptoms of ADHD when compared to the 10/10 genotype [111], whilst others pinpoint association with susceptibility to ADHD with the presence of a 10 repeat allele in family transmission studies [112][113][114][115][116][117]. In contrast, some studies found no association between DAT1 polymorphisms and ADHD using either family based [118,119] or population based studies [120,121]. However, a role for the DAT1 transporter in ADHD is strongly supported by the facts that DAT1 knockout mice are extremely hyperactive [122] and that current therapies for ADHD include drugs that act on the transporter e.g., methylphenidate (Ritalin).…”

Dopamine Transporter (SLC6A3) Genotype Impacts Neurophysiological Correlates of Cognitive Response Control in an Adult Sample of Patients with ADHD

“…However, findings are heterogeneous and may depend on the specific statistical analysis method (Todd et al, 2005;Li et al, 2006;Yang et al, 2007;Langley et al, 2005;Cheuk et al, 2006). Furthermore, in adult samples, the nine-repeat allele has been shown to be associated with the disease, suggesting a differential association depending on age, and a role of SLC6A3 in modulating the ADHD phenotype over life time (Franke et al, 2008(Franke et al, , 2010.…”