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Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Sengupta, Sarojini M. Grizenko, Natalie Thakur, Geeta A. Bellingham, Johanne DeGuzman, Rosherrie Robinson, Sandra Ter-Stepanian, Marina Poloskia, Anna Shaheen, Sara Fortier, Marie-Ève Choudhry, Zia Joober, Ridha |
| Copyright Year | 2012 |
| Abstract | BACKGROUND Pharmacologic and animal studies have strongly implicated the norepinephrine transporter (NET) in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We conducted a family-based study, with stratification based on sex and subtype, to test the association between 30 tag single-nucleotide polymorphisms (SNPs) within the gene encoding NET (SLC6A2) and ADHD. METHODS Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT. RESULTS A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplo-type block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2. LIMITATIONS The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype. CONCLUSION The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples. |
| File Format | PDF HTM / HTML |
| DOI | 10.1503/jpn.110073 |
| PubMed reference number | 22297068 |
| Journal | Medline |
| Volume Number | 37 |
| Issue Number | 2 |
| Alternate Webpage(s) | http://jpn.ca/wp-content/uploads/2014/04/37-2-129.pdf |
| Alternate Webpage(s) | https://doi.org/10.1503/jpn.110073 |
| Journal | Journal of psychiatry & neuroscience : JPN |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
