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DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD): Effects of associated alleles at the VNTR and −521 SNP
Author(s) -
Bellgrove Mark A.,
Hawi Ziarih,
Lowe Naomi,
Kirley Aiveen,
Robertson Ian H.,
Gill Michael
Publication year - 2005
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30193
Subject(s) - allele , genetics , attention deficit hyperactivity disorder , proband , snp , single nucleotide polymorphism , biology , heterozygote advantage , allele frequency , gene , psychology , genotype , mutation , psychiatry
Abstract Associations between attention deficit hyperactivity disorder (ADHD) and genetic variants within the dopamine D4 receptor gene have been much reported. Variants investigated include the 7‐repeat allele of a VNTR within the third exon, and two SNPs (−521 and −616) located with the promoter region. We investigated the relationship between the VNTR, −521, and −616 SNPs and sustained attention performance in 54 ADHD probands, relative to a non‐genotyped control group. Participants performed the Sustained Attention to Response Task (SART) in which the response to an unpredictably occurring target digit must be inhibited. This task, therefore, challenged sustained attention and included a response inhibition component. Consistent with previous reports, ADHD participants possessing the 7‐repeat allele of the VNTR outperformed those children not possessing this allele, both in terms of errors and response variability. In family based analyses, better performance on the SART tended to predict biased transmission of the 7‐repeat allele from heterozygous parents. For the −521 SNP, A allele homozygotes showed greater impairment than heterozygotes or those not possessing this allele, both in terms of total errors and response variability. Family based analysis showed that higher total errors on the SART predicted transmission of the A allele from heterozygous parents. There were no effects of the −616 SNP. Our results suggest dissociable effects of the “associated alleles” of DRD4 gene variants on sustained attention: while the 7‐repeat allele of the VNTR is associated with relatively better performance, the A allele of the −521 SNP is associated with poorer performance. © 2005 Wiley‐Liss, Inc.