Treble-Barna Amery, Wade Shari L, Martin Lisa J, Pilipenko Valentina, Yeates Keith Owen, Taylor H Gerry, Kurowski Brad G
1 Division of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
2 Division of Physical Medicine and Rehabilitation, Department of Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
J Neurotrauma. 2017 Jun 1;34(11):1919-1931. doi: 10.1089/neu.2016.4840. Epub 2017 Mar 21.
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3.5 and 7 years after injury. Thirty-two single nucleotide polymorphisms (SNPs) in dopamine-related genes (dopamine receptor D2 [DRD2], solute carrier family 6 member 3 [SLC6A3], solute carrier family 18 member A2 [SLC18A2], catechol-o-methyltransferase [COMT], and ankyrin repeat and kinase domain containing 1 [ANKK1]) were examined in association with short- and long-term executive function and behavioral adjustment, as well as their trajectories over time. After controlling for premorbid child functioning, genetic variation within the SLC6A3 (rs464049 and rs460000) gene was differentially associated with neurobehavioral recovery trajectories over time following TBI relative to OI, with rs464049 surviving multiple testing corrections. In addition, genetic variation within the ANKK1 (rs1800497 and rs2734849) and SLC6A3 (rs464049, rs460000, and rs1042098) genes was differentially associated with short- and long-term neurobehavioral recovery following TBI, with rs460000 and rs464049 surviving multiple testing corrections. The findings provide preliminary evidence that genetic variation in genes involved in DRD2 expression and density (ANKK1) and dopamine transport (SLC6A3) plays a role in neurobehavioral recovery following pediatric TBI.
本研究调查了多巴胺相关基因与幼儿期创伤性脑损伤（TBI）儿童相对于骨科损伤（OI）儿童的短期和长期神经行为恢复以及随时间变化的神经行为恢复轨迹之间的关联。参与者来自一项前瞻性纵向研究，该研究评估了3至7岁期间遭受TBI（n = 68）或OI（n = 72）的儿童的结局。父母在急性后期（受伤后0至3个月）、受伤后6、12和18个月以及受伤后平均3.5年和7年完成对儿童执行功能和行为的评分。研究检测了多巴胺相关基因（多巴胺受体D2 [DRD2]、溶质载体家族6成员3 [SLC6A3]、溶质载体家族18成员A2 [SLC18A2]、儿茶酚-O-甲基转移酶 [COMT] 和含锚蛋白重复序列和激酶结构域1 [ANKK1]）中的32个单核苷酸多态性（SNP）与短期和长期执行功能及行为调整以及它们随时间的轨迹之间的关联。在控制了病前儿童功能后，与OI相比，SLC6A3基因（rs464049和rs460000）内的基因变异与TBI后随时间变化的神经行为恢复轨迹存在差异关联，其中rs464049在多次检验校正后仍显著。此外，ANKK1基因（rs1800497和rs2734849）和SLC6A3基因（rs464049、rs460000和rs1042098）内的基因变异与TBI后的短期和长期神经行为恢复存在差异关联，其中rs460000和rs464049在多次检验校正后仍显著。这些发现提供了初步证据，表明参与DRD2表达和密度（ANKK1）以及多巴胺转运（SLC6A3）的基因中的基因变异在小儿TBI后的神经行为恢复中起作用。
