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Association between genetic polymorphisms of synaptophysin (SYP) gene and attention deficit hyperactivity disorder in Korean subjects

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Abstract

Background

Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder, and the prevalence of ADHD among Korean children has attained about 8.5%. Various genetic factors can contribute to the etiology of the disease. Synaptophysin (SYP) regulates neurotransmitter release and synaptic plasticity. According to previous studies, several genetic polymorphisms on SYP were risk factors for ADHD.

Objective

We investigated the effect of the SYP gene polymorphisms (rs2293945 and rs3817678) on ADHD in Korean children.

Methods

In this study, we examined the case-control study in 150 ADHD cases and 322 controls. The genotyping of SYP gene polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

Significant associations in the genotype and genetic models of SYP rs2293945 polymorphism between girls with ADHD and control girls were found. The girls with ADHD having the C/T genotype were significantly associated with ADHD. In the dominant model of rs3817678, C/T + T/T genotypes were significantly associated with ADHD. The haplotype analyses showed significant associations from haplotypes of rs2293945 T-rs3817678 G and rs2293945 C-rs3817678 A.

Conclusion

Our results imply that the SYP rs2293945 C/T polymorphism in female participants may provide a possible effect on the genetic etiology of ADHD.

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References

  • Adams DJ, Arthur CP, Stowell MH (2015) Architecture of the Synaptophysin/Synaptobrevin complex: structural evidence for an entropic clustering function at the synapse. Sci Rep 5:13659. https://doi.org/10.1038/srep13659

    Article  PubMed  PubMed Central  Google Scholar 

  • Alder J, Lu B, Valtorta F, Greengard P, Poo MM (1992) Calcium-dependent transmitter secretion reconstituted in Xenopus oocytes: requirement for synaptophysin. Science 257:657–661. https://doi.org/10.1126/science.1353905

    Article  CAS  PubMed  Google Scholar 

  • Alder J, Kanki H, Valtorta F, Greengard P, Poo MM (1995) Overexpression of synaptophysin enhances neurotransmitter secretion at Xenopus neuromuscular synapses. J Neurosci 15:511–519. https://doi.org/10.1523/JNEUROSCI.15-01-00511.1995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • American Psychiatric Association Committee on Nomenclature and Statistics (1994) Diagnostic and statistical manual of mental disorders (DSM-IV), 4th edn. American Psychiatric Assocaition Press, Washington, DC

    Google Scholar 

  • Banaschewski T, Becker K, Scherag S, Franke B, Coghill D (2010) Molecular genetics of attention-deficit/hyperactivity disorder: an overview. Eur Child Adolesc Psychiatry 19:237–257. https://doi.org/10.1007/s00787-010-0090-z

    Article  PubMed  PubMed Central  Google Scholar 

  • Barkley RA (1998) Attention-deficit hyperactivity disorder. Sci Am 279:66–71. https://doi.org/10.1038/scientificamerican0998-66

    Article  CAS  PubMed  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265. https://doi.org/10.1093/bioinformatics/bth457

    Article  CAS  PubMed  Google Scholar 

  • Brookes KJ, Knight J, Xu X, Asherson P (2005) DNA pooling analysis of ADHD and genes regulating vesicle release of neurotransmitters. Am J Med Genet B Neuropsychiatr Genet 139B:33–37. https://doi.org/10.1002/ajmg.b.30216

    Article  CAS  PubMed  Google Scholar 

  • Carrel L, Willard HF (2005) X-inactivation profile reveals extensive variability in X-linked gene expression in females. Natur 434:400–404. https://doi.org/10.1038/nature03479

    Article  CAS  Google Scholar 

  • Christine Knickmeyer R, Baron-Cohen S (2006) Fetal testosterone and sex differences. Early Hum 82:755–760. https://doi.org/10.1016/j.earlhumdev.2006.09.014

    Article  CAS  Google Scholar 

  • Cremin SM, Greer WL, Bodok-Nutzati R, Schwartz M, Peacocke M, Siminovitch KA (1993) Linkage of Wiskott-Aldrich syndrome with three marker loci, DXS426, SYP and TFE3, which map to the Xp11.3-p11.22 region. Hum Genet 92:250–253. https://doi.org/10.1007/BF00244467

    Article  CAS  PubMed  Google Scholar 

  • Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayés M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DH, Bloss CS, Boehnke M, Boomsma DI, Breen G, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flickinger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisén L, Gallagher L, Gejman PV, Georgieva L, Gershon ES, Geschwind DH, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP,Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S,Hickie IB, Hipolito M, Hoefels S, Holmans PA, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng JY, Kähler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landén M, Långström N, Lathrop M, Lawrence J, Lawson WB, Leboyer M, Ledbetter DH, Lee PH, Lencz T, Lesch KP, Levinson DF, Lewis CM, Li J, Lichtenstein P, Lieberman JA, Lin DY, Linszen DH, Liu C, Lohoff FW, Loo SK, Lord C, Lowe JK, Lucae S, MacIntyre DJ, Madden PA, Maestrini E, Magnusson PK,Mahon PB, Maier W, Malhotra AK, Mane SM, Martin CL, Martin NG, Mattheisen M, Matthews K, Mattingsdal M, McCarroll SA, McGhee KA, McGough JJ, McGrath PJ, McGuffin P, McInnis MG, McIntosh A, McKinney R, McLean AW, McMahon FJ, McMahon WM, McQuillin A, Medeiros H, Medland SE, Meier S, Melle I, Meng F, Meyer J, Middeldorp CM, Middleton L, Milanova V, Miranda A, Monaco AP, Montgomery GW, Moran JL, Moreno-De-Luca D, Morken G, Morris DW, Morrow EM, Moskvina V, Muglia P, Mühleisen TW, Muir WJ, Müller-Myhsok B, Murtha M, Myers RM, Myin-Germeys I, Neale MC, Nelson SF, Nievergelt CM, Nikolov I, Nimgaonkar V, Nolen WA, Nöthen MM, Nurnberger JI, Nwulia EA, Nyholt DR, O’Dushlaine C, Oades RD, Olincy A, Oliveira G, Olsen L, Ophoff RA, Osby U, Owen MJ, Palotie A, Parr JR,Paterson AD, Pato CN, Pato MT, Penninx BW, Pergadia ML, Pericak-Vance MA, Pickard BS, Pimm J, Piven J, Posthuma D, Potash JB, Poustka F, Propping P, Puri V, Quested DJ, Quinn EM, Ramos-Quiroga JA, Rasmussen HB, Raychaudhuri S, Rehnström K, Reif A,Ribasés M, Rice JP, Rietschel M, Roeder K, Roeyers H, Rossin L, Rothenberger A, Rouleau G, Ruderfer D, Rujescu D, Sanders AR, Sanders SJ, Santangelo SL, Sergeant JA, Schachar R, Schalling M, Schatzberg AF, Scheftner WA, Schellenberg GD, Scherer SW, Schork NJ,Schulze TG, Schumacher J, Schwarz M, Scolnick E, Scott LJ, Shi J, Shilling PD, Shyn SI, Silverman JM, Slager SL, Smalley SL, Smit JH, Smith EN, Sonuga-Barke EJ, St Clair D, State M, Steffens M, Steinhausen HC, Strauss JS, Strohmaier J, Stroup TS, Sutcliffe JS, Szatmari P, Szelinger S, Thirumalai S, Thompson RC, Todorov AA, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Van Os J, Vicente AM, Vieland VJ, Vincent JB, Visscher PM, Walsh CA, Wassink TH, Watson SJ, Weissman MM, Werge T, Wienker TF,Wijsman EM, Willemsen G, Williams N, Willsey AJ, Witt SH, Xu W, Young AH, Yu TW, Zammit S, Zandi PP, Zhang P, Zitman FG, Zöllner S, Devlin B, Kelsoe JR, Sklar P, Daly MJ,O’Donovan MC, Craddock N, Sullivan PF, Smoller JW, Kendler KS, Wray NR; International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) (2013) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45:984–994. https://doi.org/10.1038/ng.2711

  • Davies W (2014) Sex differences in attention deficit hyperactivity disorder: candidate genetic and endocrine mechanisms. Front Neuroendocrinol 35:331–346. https://doi.org/10.1016/j.yfrne.2014.03.003

    Article  CAS  PubMed  Google Scholar 

  • DuPaul GJ, Power TJ, Anastopoulos AD, Reid R, McGoey KE, Ikeda MJ (1997) Teacher ratings of attention deficit hyperactivity disorder symptoms: factor structure and normative data. Psycholo Assess 9:436–444. https://doi.org/10.1037/1040-3590.9.4.436

    Article  Google Scholar 

  • Faraone SV (2004) Genetics of adult attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 27:303–321. https://doi.org/10.1016/S0193-953X(03)00090-X

    Article  PubMed  Google Scholar 

  • Faraone SV, Doyle AE (2001) The nature and heritability of attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 10:299–316 PMID: 11351800

    Article  CAS  PubMed  Google Scholar 

  • Flemming A (2012) Stroke: can PSD95 inhibitors widen the therapeutic window? Nat Rev Drug Discov 11:272. https://doi.org/10.1038/nrd3716

    Article  CAS  PubMed  Google Scholar 

  • Franke B, Neale BM, Faraone SV (2009) Genome-wide association studies in ADHD. Hum Genet 126:13–50. https://doi.org/10.1007/s00439-009-0663-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Q, Liu L, Li HM, Tang YL, Wu ZM, Chen Y, Wang YF, Qian QJ (2015) Interactions between MAOA and SYP polymorphisms were associated with symptoms of attention-deficit/hyperactivity disorder in chinese Han subjects. Am J Med Genet B Neuropsychiatr Genet 168B:45–53. https://doi.org/10.1002/ajmg.b.32273

    Article  CAS  PubMed  Google Scholar 

  • Gaub M, Carlson CL (1997) Behavioral characteristics of DSM-IV ADHD subtypes in a school-based population. J Abnorm Child Psychol 25:103–111. https://doi.org/10.1023/a:1025775311259

    Article  CAS  PubMed  Google Scholar 

  • Guan L, Wang B, Chen Y, Yang L, Li J, Qian Q, Wang Z, Faraone SV, Wang Y (2009) A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among chinese Han population. Mol Psychiatry 14:546–554. https://doi.org/10.1038/sj.mp.4002139

    Article  CAS  PubMed  Google Scholar 

  • Hawi Z, Cummins TD, Tong J, Johnson B, Lau R, Samarrai W, Bellgrove MA (2015) The molecular genetic architecture of attention deficit hyperactivity disorder. Mol Psychiatry 20:289–297. https://doi.org/10.1038/mp.2014.183

    Article  CAS  PubMed  Google Scholar 

  • Hong JH, Hwang IW, Lim MH, Kwon HJ, Jin HJ (2018) Genetic associations between ADHD and dopaminergic genes (DAT1 and DRD4) VNTRs in korean children. Genes Genomics 40:1309–1317. https://doi.org/10.1007/s13258-018-0726-9

    Article  CAS  PubMed  Google Scholar 

  • Hwang IW, Lim MH, Kwon HJ, Jin HJ (2018) Association of Monoamine Oxidase A (MAOA) Gene uVNTR and rs6323 polymorphisms with attention deficit and hyperactivity disorder in Korean Children. Med (Kaunas) 54:32. https://doi.org/10.3390/medicina54030032

    Article  Google Scholar 

  • Kim YS, Woo J, Lee CJ, Yoon BE (2017) Decreased glial GABA and Tonic Inhibition in Cerebellum of Mouse Model for Attention-Deficit/Hyperactivity disorder (ADHD). Exp Neurobiol 26:206–212. https://doi.org/10.5607/en.2017.26.4.206

    Article  PubMed  PubMed Central  Google Scholar 

  • Kwon HJ, Lee MY, Ha M, Yoo SJ, Paik KC, Lim JH, Sakong J, Lee CG, Kang DM, Hong SJ, Cho HI, Lim MH (2014) The associations between ADHD and asthma in korean children. BMC Psychiatry 14:70. https://doi.org/10.1186/1471-244X-14-70

    Article  PubMed  PubMed Central  Google Scholar 

  • Lahey BB, Pelham WE, Stein MA, Loney J, Trapani C, Nugent K, Kipp H, Schmidt E, Lee S, Cale M, Gold E, Hartung CM, Willcutt E, Baumann B (1998) Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children. J Am Acad Child Adolesc Psychiatry 37:695–702. https://doi.org/10.1097/00004583-199807000-00008

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Chen Y, Li H, Qian Q, Yang L, Glatt SJ, Faraone SV, Wang Y (2013) Association between SYP with attention-deficit/hyperactivity disorder in chinese Han subjects: differences among subtypes and genders. Psychiatry Res 210:308–314. https://doi.org/10.1016/j.psychres.2013.04.029

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Liu B, Yuan P, Cheng L, Sun H, Gui J, Pan Y, Huang D, Chen H, Jiang L (2021) Role of PKA/CREB/BDNF signaling in PM2.5-induced neurodevelopmental damage to the hippocampal neurons of rats. Ecotoxicol Environ Saf 214:112005. https://doi.org/10.1016/j.ecoenv.2021.112005

    Article  CAS  PubMed  Google Scholar 

  • Ma J, Zhang Z, Kang L, Geng D, Wang Y, Wang M, Cui H (2014) Repetitive transcranial magnetic stimulation (rTMS) influences spatial cognition and modulates hippocampal structural synaptic plasticity in aging mice. Exp Gerontol 58:256–268. https://doi.org/10.1016/j.exger.2014.08.011

    Article  PubMed  Google Scholar 

  • Maciejewska-Karlowska A, Hanson ED, Sawczuk M, Cieszczyk P, Eynon N (2014) Genomic haplotype within the peroxisome proliferator-activated receptor Delta (PPARD) gene is associated with elite athletic status. Scand J Med Sci Sports 24:e148–e155. https://doi.org/10.1111/sms.12126

    Article  CAS  PubMed  Google Scholar 

  • Mick E, Todorov A, Smalley S, Hu X, Loo S, Todd RD, Biederman J, Byrne D, Dechairo B, Guiney A, McCracken J, McGough J, Nelson SF, Reiersen AM, Wilens TE, Wozniak J, Neale BM, Faraone SV (2010) Family-based genome-wide association scan of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49:898–905e3. https://doi.org/10.1016/j.jaac.2010.02.014

    Article  PubMed  PubMed Central  Google Scholar 

  • Morgan AE, Hynd GW, Riccio CA, Hall J (1996) Validity of DSM-IV ADHD predominantly inattentive and combined types: relationship to previous DSM diagnoses/subtype differences. J Am Acad Child Adolesc Psychiatr 35:325–333. https://doi.org/10.1097/00004583-199603000-00014

    Article  CAS  Google Scholar 

  • Sánchez-Mora C, Cormand B, Ramos-Quiroga JA, Hervás A, Bosch R, Palomar G, Nogueira M, Gómez-Barros N, Richarte V, Corrales M, Garcia-Martinez I, Corominas R, Guijarro S, Bigorra A, Bayés M, Casas M, Ribasés M (2013) Evaluation of common variants in 16 genes involved in the regulation of neurotransmitter release in ADHD. Eur Neuropsychopharmacol 23:426–435. https://doi.org/10.1016/j.euroneuro.2012.07.014

    Article  CAS  PubMed  Google Scholar 

  • Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (2012) Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatry 51:1003–1019e20. https://doi.org/10.1016/j.jaac.2012.08.015

    Article  PubMed  Google Scholar 

  • Schachar R (2014) Genetics of attention deficit hyperactivity disorder (ADHD): recent updates and future prospects. Curr Dev Disord Rep 1:41–49. https://doi.org/10.1007/s40474-013-0004-0

    Article  Google Scholar 

  • Shen YC, Tsai HM, Ruan JW, Liao YC, Chen SF, Chen CH (2012) Genetic and functional analyses of the gene encoding synaptophysin in schizophrenia. Schizophr Res 137:14–19. https://doi.org/10.1016/j.schres.2012.01.028

    Article  PubMed  Google Scholar 

  • Sims KB, Lebo RV, Benson G, Shalish C, Schuback D, Chen ZY, Bruns G, Craig IW, Golbus MS, Breakefield XO (1992) The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3. Hum Mol Genet 1:83–89. https://doi.org/10.1093/hmg/1.2.83

    Article  CAS  PubMed  Google Scholar 

  • So YK, Noh JS, Kim YS, Ko SG, Koh YJ (2002) The reliability and validity of korean parent and teacher ADHD rating scale. J Korean Neuropsychiatr Assoc 41:283–289

    Google Scholar 

  • Suresh K, Chandrashekara S (2012) Sample size estimation and power analysis for clinical research studies. J Hum Reprod Sci 5:7–13. https://doi.org/10.4103/0974-1208.97779

    Article  PubMed  PubMed Central  Google Scholar 

  • Tarver J, Daley D, Sayal K (2014) Attention-deficit hyperactivity disorder (ADHD): an updated review of the essential facts. Child Care Health Dev 40:762–774. https://doi.org/10.1111/cch.12139

    Article  CAS  PubMed  Google Scholar 

  • Trent S, Davies W (2012) The influence of sex-linked genetic mechanisms on attention and impulsivity. Biol Psychol 89:1–13. https://doi.org/10.1016/j.biopsycho.2011.09.011

    Article  PubMed  PubMed Central  Google Scholar 

  • Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JA (2007) Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res 35:W71–W74. https://doi.org/10.1093/nar/gkm306

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu MV, Manoli DS, Fraser EJ, Coats JK, Tollkuhn J, Honda S, Harada N, Shah NM (2009) Estrogen masculinizes neural pathways and sex-specific behaviors. Cell 139:61–72. https://doi.org/10.1016/j.cell.2009.07.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao YH, Wang ZF, Cao CJ, Weng H, Xu CS, Li K, Li JL, Lan J, Zeng XT, Li ZQ (2018) The clinical significance of O6-Methylguanine-DNA methyltransferase promoter methylation status in adult patients with glioblastoma: a Meta-analysis. Front Neurol 9:127. https://doi.org/10.3389/fneur.2018.00127

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Research Foundation of Korea Grant funded by the Korea Government (NRF- 2019R1D1A3A03103804).

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  1. Department of Biological Science, College of Science & Technology, Dankook University, 31116, Cheonan, South Korea

    Hyung Jun Kim, Seong Yong Kim, Ga Eun Kim & Han Jun Jin

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Kim, H.J., Kim, S.Y., Kim, G.E. et al. Association between genetic polymorphisms of synaptophysin (SYP) gene and attention deficit hyperactivity disorder in Korean subjects. Genes Genom 45, 1097–1105 (2023). https://doi.org/10.1007/s13258-023-01393-7

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