Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
Institute of Psychiatry-Center of Excellence, Institute of Post Graduate Medical Education & Research, Kolkata, West Bengal 700020, India.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):1-10. doi: 10.1016/j.pnpbp.2018.01.016. Epub 2018 Jan 31.
An etiologically complex disorder, Attention Deficit Hyperactivity Disorder (ADHD), is often associated with various levels of cognitive deficit. Folate/vitamin B is crucial for numerous biochemical pathways including neural stem cell proliferation and differentiation, regulation of gene expression, neurotransmitter synthesis, myelin synthesis and repair, etc. and a scarcity has often been linked to cognitive deficit. Our pilot study in the field revealed significant association of few genetic variants with ADHD. Mild hyperhomocysteinemia and vitamin B deficiency was also noticed in the probands. In the present study additional genetic variants, folate and vitamin B, which may affect folate-homocysteine metabolic pathway, were investigated in 866 individuals including nuclear families with ADHD probands (N=221) and ethnically matched controls (N=286) to find out whether ADHD associated traits are affected by these factors. Population based analysis revealed significant over representation of MTRR rs1801394 "G" allele and "GG" genotype in all as well as male probands. Stratified analysis showed significantly higher frequency of RFC1 rs1051266 and BHMT rs3733890 "AG" genotypes in full term and prematurely delivered ADHD probands respectively. Probands with rs1801394 "GG" genotype and BHMT rs3733890 "G" allele showed association with hyperhomocysteinemia. MTHFR rs1801131, MTR rs1805087 and BHMT rs3733890 also showed association with ADHD index. While rs1051266, rs1801131, and rs1805087 showed association with behavioral problems, rs3733890 was associated with ODD score. Conduct problem exhibited association with RFC1 rs1051266, MTHFR rs1801133 and MTRR rs1801394. Gene-gene interaction analysis revealed positive synergistic interactions between rs1051266, rs1801131 and rs1801394 in the probands as compared to the controls. It can be inferred from the data obtained that folate system genetic variants and mild hyperhomocysteimenia may affect ADHD associated traits by attenuating folate metabolism.
注意缺陷多动障碍（ADHD）是一种病因复杂的疾病，常伴有各种程度的认知缺陷。叶酸/维生素 B 对许多生化途径至关重要，包括神经干细胞增殖和分化、基因表达调控、神经递质合成、髓鞘合成和修复等，而其缺乏往往与认知缺陷有关。我们在该领域的初步研究表明，少数遗传变异与 ADHD 显著相关。在患者中还注意到轻度高同型半胱氨酸血症和维生素 B 缺乏。在本研究中，我们调查了叶酸和维生素 B 等其他遗传变异，这些变异可能影响叶酸-同型半胱氨酸代谢途径，共纳入 866 名个体，包括 ADHD 患者（N=221）及其同种族匹配的对照（N=286）的核心家庭，以确定这些因素是否影响与 ADHD 相关的特征。基于人群的分析显示，MTRR rs1801394“G”等位基因和“GG”基因型在所有患者和男性患者中均过度表达。分层分析显示，足月和早产 ADHD 患者的 RFC1 rs1051266 和 BHMT rs3733890“AG”基因型的频率显著升高。携带 rs1801394“GG”基因型和 BHMT rs3733890“G”等位基因的患者与高同型半胱氨酸血症相关。MTHFR rs1801131、MTR rs1805087 和 BHMT rs3733890 也与 ADHD 指数相关。rs1051266、rs1801131 和 rs1805087 与行为问题相关，rs3733890 与 ODD 评分相关。品行问题与 RFC1 rs1051266、MTHFR rs1801133 和 MTRR rs1801394 相关。基因-基因相互作用分析显示，与对照组相比，患者中 rs1051266、rs1801131 和 rs1801394 之间存在正协同相互作用。从获得的数据可以推断，叶酸系统遗传变异和轻度高同型半胱氨酸血症可能通过减弱叶酸代谢来影响与 ADHD 相关的特征。
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