Meta-analysis on the association between brain derived neurotrophic factor Val66Met gene polymorphism and attention deficit hyperactivity disorder

doi:10.11852/zgetbjzz2020-1952

Abstract

Abstract: Objective To evaluate the association between brain derived neurotrophic factor (BDFN) Val66Met gene polymorphism and attention deficit/hyperactivity disorder (ADHD), in order to provide clues for research on genetic etiology of ADHD. Methods The CNKI, WanFang, PubMed, EMbase and Web of Science databases were conducted to collect published case-control studies on the association between Val66Met and ADHD from establishment to April 2020.Two reviewers independently screened the literature, extracted the data, and assessed the quality of included studies.RevMan 5.3 and Stata 11.0 software then were used to perform meta-analysis. Results Totally 9 articles were included with 8 458 samples (including 4 247 cases and 4 211 controls).Meta-analysis indicated that rs6265 was not associated with the susceptibility to ADHD (dominant gene model: OR=0.96, 95%CI:0.87 - 1.06, P=0.40 ; recessive model: OR=1.01, 95%CI:0.88 - 1.15, P=0.92; additive model: OR=0.95,95%CI:0.85 - 1.08,P=0.45). Conclusion The polymorphism of BDNF Val66Met gene is not associated with susceptibility to ADHD.

Key words: brain derived neurotrophic factor(BDNF), Val66Met, attention deficit/hyperactivity disorder, Meta-analysis

摘要： 目的评价脑源性神经营养因子(BDFN)基因Val66Met多态性与注意缺陷多动障碍(ADHD)易感性的关系,以期为ADHD的遗传病因学研究提供线索。方法计算机检索CNKI、WanFang、PubMed、EMbase、Web of Science数据库,搜集公开发表的有关BDNF基因Val66Met多态性与ADHD易感性相关的病例对照研究,检索时限为建库至2020年4月。由2名研究者独立筛选文献、提取资料并对纳入研究进行质量评价后,采用RevMan 5.3和Stata11.0软件进行 Meta 分析。结果共纳入9篇文献,8 458例样本(其中病例4 247例,对照4 211例)。分析结果显示,rs6265多态性与注意缺陷多动障碍易感性无关(显性模型:OR=0.96,95%CI:0.87～1.06,P=0.40;隐性模型:OR=1.01,95%CI:0.88～1.15,P=0.92;加性模型:OR=0.95,95%CI:0.85～1.08,P=0.45)。结论脑源性神经营养因子基因Val66Met多态性与注意缺陷多动障碍易感性无关。

关键词: 脑源性神经营养因子, Val66Met, 注意缺陷多动障碍, Meta分析

CLC Number:

R749.94

CHEN Wen-cai, ZUO Fei-yan, WAN Ying, WANG Mei-ling. Meta-analysis on the association between brain derived neurotrophic factor Val66Met gene polymorphism and attention deficit hyperactivity disorder[J]. Chinese Journal of Child Health Care, 2022, 30(3): 301-305.

陈文材, 佐飞燕, 万莹, 王玫玲. 脑源性神经营养因子基因Val66Met多态性与注意缺陷多动障碍易感性的Meta分析[J]. 中国儿童保健杂志, 2022, 30(3): 301-305.

References

[1] 李世明, 冯为, 方芳, 等.中国儿童注意缺陷多动障碍患病率Meta分析[J].中华流行病学杂志, 2018, 39(7): 993-998.
[2] Wang T, Liu K, Li Z, et al.Prevalence of attention deficit/hyperactivity disorder among children and adolescents in China: A systematic review and meta-analysis[J].BMC Psychiatry, 2017, 17(1): 32.
[3] Faraone SV, Perlis RH, Doyle AE, et al.Molecular genetics of attention-deficit/hyperactivity Disorder[J].Biol Psychiatry, 2005, 57(11): 1313-1323.
[4] 曹银利, 唐成和, 李树军, 等.脑源性神经营养因子基因多态性与注意缺陷多动障碍的关联性研究[J].现代生物医学进展, 2011, 11(2): 317-319.
[5] Bergman O, Westberg L, Lichtenstein P, et al.Study on the possible association of brain-derived neurotrophic factor polymorphism with the developmental course of symptoms of attention deficit and hyperactivity[J].Int J Neuropsychopharmacol, 2011, 14(10): 1367-1376.
[6] Tzang RF, Hsu CD, Liou YJ, et al.Family-based association of the brain-derived neurotrophic factor gene in attention-deficit hyperactivity disorder[J].Psychiatr Genet, 2013, 23(4): 177-178.
[7] Matthew L, Alessio S, Marilee K, et al.Association study of brain-derived neurotrophic factor (BDNF) and LIN-7 homolog (LIN-7) genes with adult attention-deficit/hyperactivity disorder[J].Am J Med Genet B Neuropsychiatr Genet, 2008, 147b(6): 945-951.
[8] 曾宪涛, 刘慧, 陈曦, 等.Meta分析系列之四:观察性研究的质量评价工具[J].中国循证心血管医学杂志, 2012, 4(4): 297-299.
[9] Sánchez MC, Ribasés M, Ramos QJA, et al.Meta-analysis of brain-derived neurotrophic factor p.Val66Met in adult ADHD in four European populations[J].Am J Med Genet B Neuropsychiatr Genet, 2010, 153B(2): 512-523.
[10] Friedel S, Fontenla Horro F, Wermter AK, et al.Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder[J].Am J Med Genet B Neuropsychiatr Genet, 2005, 132B(1): 96-99.
[11] Luo L, Jiang X, Cao G, et al.Association between BDNF gene polymorphisms and attention deficit hyperactivity disorder in school-aged children in Wuhan, China[J].J Affect Disord, 2020, 264:304-309.
[12] Cho SC, Kim HW, Kim BN, et al.Gender-specific association of the brain-derived neurotrophic factor gene with attention-deficit/hyperactivity disorder[J].Psychiatry Investig, 2010, 7(4): 285-890.
[13] Kwon HJ, Ha Mina, Jin HJ, et al.Association between BDNF gene polymorphisms and attention deficit hyperactivity disorder in Korean children[J].Genet Test Mol Biomarkers, 2015, 9(7):366-371.
[14] Liu DY, Shen XM, Yuan FF, et al.The physiology of BDNF and its relationship with ADHD[J].Mol Neurobiol, 2015, 52(3):1467-1476.
[15] 李海梅, 钱秋谨, 王玉凤,等.脑源性神经营养因子基因单核苷酸多态与注意缺陷多动障碍的关系[J].实用儿科临床杂志, 2011, 26(4):277-282.
[16] Aureli A, Beato TD, Sebastiani P, et al.Attention-deficit hyperactivity disorder and intellectual disability: a study of association with brain-derived neurotrophic factor gene polymorphisms.[J].Int J Immunopathol Pharmacol, 2010, 23(3):873-880.
[17] 沈雪梅.脑源性神经营养因子遗传变异与注意缺陷多动障碍的关联研究[D]. 武汉:华中科技大学, 2015.
[18] Se HS, Young HB, Young JK, et al.Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD)[J].Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(8): 1824-1828.
[19] Lipsky RH, Marini AM.Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity[J].Ann N Y Acad Sci, 2008, 1122(1): 130-143.
[20] Yeom CW, Park YJ, Choi SW, et al.Association of peripheral BDNF level with cognition, attention and behavior in preschool children[J].Child Adolesc Psychiatry Ment Health, 2016, 10(1):1-10.
[21] Margarida CR, Ramos QJA, Marta R, et al.Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder[J].Int J Neuropsychopharmacol, 2013, 16(6): 1267-1275.
[22] Ito W, Chehab M, Thakur S, et al.BDNF-restricted knockout mice as an animal model for aggression[J].Genes Brain Behav, 2011, 10(3): 365-374.
[23] Alonso M, Vianna MRM, Izquierdo I, et al.Signaling mechanisms mediating BDNF modulation of memory formation in vivo in the hippocampus[J].Cell Mol Neurobiol, 2002, 22(5-6):663-674.
[24] Minichiello L, Korte M, Wolfer D, et al.Essential role for TrkB receptors in hippocampus-mediated learning[J].Neuron, 1999, 24(2): 401-414.
[25] Egan MF, Kojima M, Callicott JH, et al.The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function[J].Cell, 2003, 112(2): 257-269.
[26] Aureli A, Beato T D, Sebastiani P, et al.Attention-deficit hyperactivity disorder and intellectual disability: A study of association with brain-derived neurotrophic factor gene polymorphisms[J].Int J Immunopathol Pharmacol, 2010, 23(3): 873-880.
[27] Xu X, Mill J, Zhou K, et al.Family-based association study between brain-derived neurotrophic factor gene polymorphisms and attention deficit hyperactivity disorder in UK and Taiwanese samples[J].Am J Med Genet B Neuropsychiatr Genet, 2010,144B(1): 83-86.
[28] Guan L, Wang B, Chen Y, et al.A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: Suggesting multiple susceptibility genes among Chinese Han population[J].Mol Psychiatry, 2009, 14(5): 546-554.