Manovikas Biomedical Research and Diagnostic Centre, E.M. Bypass, Kolkata, India.
Sci Rep. 2017 Jul 28;7(1):6828. doi: 10.1038/s41598-017-06852-2.
Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454, rs2069456 and rs2069459, predicted to affect transcription, were found to be bimorphic. Significant difference in rs2069456 "AC" genotype frequency was noticed in the probands, more specifically in the males. Family based analysis revealed over transmission of rs2069454 "C" and rs2069456 "A" to the probands. Quantitative trait analysis exhibited association of haplotypes with inattention, domain specific impulsivity, and behavioral problem, though no significant contribution was noticed on the age of onset of ADHD. Gene variants also showed significant association with cognitive function and co-morbidity. Probands having rs2069459 "TT" showed betterment during follow up. It may be inferred from this pilot study that CDK5 may affect ADHD etiology, possibly by attenuating synaptic neurotransmission and could be a useful target for therapeutic intervention.
皮质神经元迁移和丝状肌动蛋白细胞骨架的形成，是发育、正常细胞生长和分化所必需的，受细胞周期蛋白依赖性激酶 5（Cdk5）调控。注意缺陷多动障碍（ADHD）与大脑发育迟缓有关，因此我们假设 cdk5 可能在 ADHD 中起作用。在包括 217 个 ADHD 先证者和 250 名健康志愿者在内的 848 名印度白种人中分析了 8 种功能性 CDK5 基因变异体。只有 rs2069454、rs2069456 和 rs2069459 三种变异体，预测会影响转录，被发现是双态的。在先证者中，特别是在男性中，rs2069456“AC”基因型频率存在显著差异。基于家庭的分析显示，rs2069454“C”和 rs2069456“A”向先证者的传递过度。数量性状分析显示，单体型与注意力不集中、特定领域冲动性和行为问题相关，尽管 ADHD 的发病年龄没有显著贡献。基因变异体也与认知功能和共病显著相关。携带 rs2069459“TT”的先证者在随访期间有改善。从这项初步研究中可以推断，CDK5 可能通过减弱突触神经传递来影响 ADHD 的发病机制，并且可能是治疗干预的有用靶点。
