Association studies of −3081(A/T) polymorphism of norepinephrine transporter gene with attention deficit/hyperactivity disorder in Korean population

Abstract

Recent studies showing the improvement of ADHD symptoms obtained with the highly selective noradrenergic reuptake inhibitor, atomoxetine, demonstrate that the noradrenergic system plays the role of pathophysiology in this disorder. It is revealed that the norepinephrine transporter gene (SLC6A2) is a possible candidate gene directly related to ADHD. To determine possible roles of the SLC6A2 as a susceptibility gene for ADHD, we performed the genetic association study for a functional À3081(A/T) polymorphism, located in the promoter region of SLC6A2. For the present study of association between ADHD and the SLC6A2, 103 male patients with ADHD and 103 normal male controls were randomly gathered. Significant differences were found in the allele frequencies (c 2 ¼ 5.60, P ¼ 0.02) and the odds ratio for the allele T between the ADHD and normal subjects was 1.59 (95% CI: 1.08-2.34) suggesting that T allele is critical to make the group difference. Significant group difference was also found in AA, AT, TT genotypes (c 2 ¼ 7.1, P ¼ 0.02). The odds ratio for TT and AT genotypes was 4.57 (95% CI: 2.56-8.15) and 1.96 (95% CI: 0.96-3.78), respectively. Findings in the present study provided further evidence of association between ADHD and À3081(A/T) polymorphism of SLC6A2.

No evidence for association between a functional promoter variant of the Norepinephrine Transporter gene SLC6A2 and ADHD in a family-based sample

“…This SNP was shown to downregulate the expression of SLC6A2 significantly, representing a very interesting candidate for molecular genetic studies in ADHD. In contrast to the results reported by Kim et al (2006) and Joung et al (2010) and in line with the findings of Cho et al (2008), we did not detect significant transmission disequilibrium for the T-allele in our sample (Kim et al 2006;Joung et al 2010;Cho et al 2008). Our study is based on family data and provides robust results against stratification admixture in contrast to case-control studies.…”

“…Though Kim et al (2008) further underlined the importance of SLC6A2 in ADHD by an extended association study, the T-3081A variant was not included in the set of investigated variants. In a recent combined case-control and family-based study on Korean children affected by ADHD, Cho et al (2008) were not able to confirm the association for the T-3081A SNP, while Joung et al reported association in a further Korean sample with relatively high odds ratios (Cho et al 2008;Joung et al 2010).…”

“…Several studies investigated the association between genetic variants of SLC6A2 and ADHD with divergent results (Brookes et al 2006;Retz et al 2008;Xu et al 2005;Bobb et al 2005;Kim et al 2008;Kim et al 2010;Joung et al 2010), while an a priori gene analysis of genome-wide association data pointed to SLC6A2 as one of the most promising candidates (Lasky-Su et al 2008). However, most of the studies have been focussing on polymorphisms whose capacity to influence the functionality of SLC6A2 is not clarified yet.…”

“…In this study, we focussed on this functionally relevant SNP in the promoter of SLC6A2 and aimed to replicate the results of Kim et al (2006) and Joung et al (2010) in a family-based ADHD sample with 162 families of German descent. To detect the odds ratio reported by Kim and colleagues, our sample provides a power of more than 99%.…”

Association of norepinephrine transporter (NET, SLC6A2) genotype with ADHD-related phenotypes: Findings of a longitudinal study from birth to adolescence

“…The human NET gene [solute carrier family 6 (neurotransmitter transporter), member 2 (norepinephrine transporter; SLC6A2)] maps to chromosome 16 (16q12.2) and consists of 16 exons (Porzgen et al, 1995), encoding for a protein of 617 amino-acids (Gelernter et al, 1993). So far, reports on potential associations between specific single nucleotide polymorphisms (SNPs) of the NET gene and ADHD or related phenotypes have been controversial (Barr et al, 2002;Bobb et al, 2005;Brookes et al, 2006;Cho et al, 2008;Joung et al, 2010;Kim et al, 2006Kim et al, , 2008bMcEvoy et al, 2002;Renner et al, 2011;Xu et al, 2005).…”