کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2494356 1556659 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel and functional norepinephrine transporter protein variants identified in attention-deficit hyperactivity disorder
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Novel and functional norepinephrine transporter protein variants identified in attention-deficit hyperactivity disorder
چکیده انگلیسی

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable disorder of impaired behavioral inhibition, increased motor activity, and inattention. The norepinephrine transporter (NET, SLC6A2) represents an important candidate gene for contribution to ADHD because it regulates catecholamine extracellular and tissue concentrations and contributes to executive functions disrupted in ADHD, and NET is a target for most effective ADHD therapeutics. We identified four NET coding single nucleotide polymorphisms (SNPs) in two ADHD sample sets; two SNPs produce protein variants (T283M, V245I), one of which, T283M, is a novel variant. Examination of the maternal family members through whom the T283M mutation was transmitted, provided no additional ADHD diagnoses. Given the previous identification of a NET mutation that contributes to a familial tachycardia syndrome, we examined autonomic function to reveal in the proband the highest standing-induced increase in heart rate among the ADHD subjects examined. We measured [3H]NE and [3H]dopamine transport for T283M, V245I, and a previously identified NET variant, T283R. T283M and V245I demonstrated decreased substrate transport, as did T283R, suggesting that the T283 residue is sensitive to mutation. Identification of polymorphic sites within NET, specifically those that produce functional consequences, is one critical step in elucidating the genetic variation contributing to the heritable component of diseases such as ADHD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 57, Issues 7–8, December 2009, Pages 694–701
نویسندگان
, , , , ,