Genetic and Epigenetic MTHFR Gene Variants in the Mothers of Attention-Deficit/Hyperactivity Disorder Affected Children as Possible Risk Factors for Neurodevelopmental Disorders

References

• Biederman J . Attention-deficit/hyperactivity disorder: a selective overview. Biol. Psychiatry57(11), 1215–1220 (2005).
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders (DSM-5).American Psychiatric Publication, DC, USA (2013).
   Google Scholar
• Spencer TJ . ADHD and comorbidity in childhood. J. Clin. Psychiatry67(Suppl. 8), S27–S31 (2006).
   PubMed Web of Science ®Google Scholar
• Hayman V , FernandezTV. Genetic insights into ADHD biology. Front. Psychiatry9, 251 (2018).
   PubMed Web of Science ®Google Scholar
• Faraone SV , PerlisRH , DoyleAEet al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol. Psychiatry57(11), 1313–1323 (2005).
   PubMed Web of Science ®Google Scholar
• Faraone SV , MickE. Molecular genetics of attention-deficit/hyperactivity disorder. Psychiatr. Clin. North Am.33(1), 159–180 (2010).
   PubMed Web of Science ®Google Scholar
• Georgieff MK , TranPV , CarlsonES. Atypical fetal development: fetal alcohol syndrome, nutritional deprivation, teratogens and risk for neurodevelopmental disorders and psychopathology. Dev. Psychopathol.30(3), 1063–1086 (2018).
   PubMed Web of Science ®Google Scholar
• Rice F , LangleyK , WoodfordC , DaveySmith G , ThaparA. Identifying the contribution of prenatal risk factors to offspring development and psychopathology: what designs to use and a critique of literature on maternal smoking and stress in pregnancy. Dev. Psychopathol.30(3), 1107–1128 (2018).
   PubMed Web of Science ®Google Scholar
• Saez M , BarcelóMA , FarreronsM , López-CasasnovasG. The association between exposure to environmental factors and the occurrence of attention-deficit/hyperactivity disorder (ADHD). A population-based retrospective cohort study. Environ. Res.166, 205–214 (2018).
   PubMed Web of Science ®Google Scholar
• Blaise SA , NédélecE , SchroederHet al. Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats. Am. J. Pathol.170(2), 667–679 (2007).
   PubMed Web of Science ®Google Scholar
• Craciunescu CN , BrownEC , MarMH , AlbrightCD , NadeauMR , ZeiselSH. Folic acid deficiency during late gestation decreases progenitor cell proliferation and increases apoptosis in fetal mouse brain. J. Nutr.134(1), 162–166 (2004).
   PubMed Web of Science ®Google Scholar
• Pulikkunnel ST , ThomasSV. Neural tube defects: pathogenesis and folate metabolism. J. Assoc. Physicians India53, 127–135 (2005).
   PubMedGoogle Scholar
• Christensen B , RosenblattDS. Effects of folate deficiency on embryonic development. Baillieres Clin. Haematol.8(3), 617–637 (1995).
   PubMedGoogle Scholar
• Schlotz W , JonesA , PhillipsDIet al. Lower maternal folate status in early pregnancy is associated with childhood hyperactivity and peer problems in offspring. J. Child Psychol. Psychiatry51(5), 594–602 (2010).
   PubMed Web of Science ®Google Scholar
• DeVilbiss EA , GardnerRM , NewschafferCJ , LeeBK. Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence. Br. J. Nutr.114(5), 663–672 (2015).
   PubMed Web of Science ®Google Scholar
• Reynolds EH . The neurology of folic acid deficiency. Handb. Clin. Neurol.120, 927–943 (2014).
   PubMedGoogle Scholar
• Wagner C . Biochemical role of folate in cellular metabolism. In: Folate in Health and Disease. BaileyLB ( Ed.). Marcel Dekker, NY, USA, 23–42 (1995).
   Google Scholar
• Crider KS , YangTP , BerryRJ , BaileyLB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv. Nutr.3(1), 21–38 (2012).
   PubMed Web of Science ®Google Scholar
• Stover PJ . Polymorphisms in 1-carbon metabolism, epigenetics and folate-related pathologies. J. Nutrigenet. Nutrigenomics4(5), 293–305 (2011).
   PubMedGoogle Scholar
• Lintas C . Linking genetics to epigenetics: the role of folate and folate-related pathways in neurodevelopmental disorders. Clin. Genet.95(2), 241–252 (2019).
   PubMed Web of Science ®Google Scholar
• Hu WF , ChahrourMH , WalshCA. The diverse genetic landscape of neurodevelopmental disorders. Annu. Rev. Genomics Hum. Genet.15, 195–213 (2014).
   PubMed Web of Science ®Google Scholar
• Lister R , MukamelEA , NeryJRet al. Global epigenomic reconfiguration during mammalian brain development. Science341(6146), 1237905 (2013).
   PubMed Web of Science ®Google Scholar
• Watanabe D , SuetakeI , TadaT , TajimaS. Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech. Dev.118(1–2), 187–190 (2002).
   PubMed Web of Science ®Google Scholar
• Liew SC , GuptaED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur. J. Med. Genet.58(1), 1–10 (2015).
   PubMed Web of Science ®Google Scholar
• van der Put NM , GabreëlsF , StevensEMet al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am. J. Hum. Genet. 62(5), 1044–1051 (1998).
   PubMed Web of Science ®Google Scholar
• Oztuzcu S , ErgunS , UlaşlıMet al. Evaluation of Factor V G1691A, prothrombin G20210A, Factor XIII V34L, MTHFR A1298C, MTHFR C677T and PAI-1 4G/5G genotype frequencies of patients subjected to cardiovascular disease (CVD) panel in south-east region of Turkey. Mol. Biol. Rep.41(6), 3671–3676 (2014).
   PubMed Web of Science ®Google Scholar
• Mansoori N , TripathiM , LuthraKet al. MTHFR (677 and 1298) and IL-6-174 G/C genes in pathogenesis of Alzheimer’s and vascular dementia and their epistatic interaction. Neurobiol. Aging33(5), 1003 (2012).
   Web of Science ®Google Scholar
• An XK , LuCX , MaQLet al. Association of MTHFR C677T polymorphism with susceptibility to migraine in the Chinese population. Neurosci. Lett.549, 78–81 (2013).
   PubMed Web of Science ®Google Scholar
• Ferrara M , CapozziL , RussoR. Impact of the MTHFR C677T polymorphism on risk of Wilms tumor: case–control study. J. Pediatr. Hematol. Oncol.31(4), 256–258 (2009).
   PubMed Web of Science ®Google Scholar
• Wan L , LiY , ZhangZ , SunZ , HeY , LiR. Methylenetetrahydrofolate reductase and psychiatric diseases. Transl. Psychiatry8(1), 242 (2018).
   PubMed Web of Science ®Google Scholar
• Asim A , AgarwalS , PanigrahiI , SaiyedN , BakshiS. MTHFR promoter hypermethylation may lead to congenital heart defects in Down syndrome. Intractable Rare Dis. Res.6(4), 295–298 (2017).
   PubMedGoogle Scholar
• Rotondo JC , BosiS , BazzanEet al. Methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples of infertile couples correlates with recurrent spontaneous abortion. Hum. Reprod.27(12), 3632–3638 (2012).
   PubMed Web of Science ®Google Scholar
• Saraswathy KN , KaurL , TalwarSet al. Methylenetetrahydrofolate reductase gene-specific methylation and recurrent miscarriages: a case-control study from North India. J. Hum. Reprod. Sci.11(2), 142–147 (2018).
   PubMedGoogle Scholar
• Jiménez KM , Pereira-MoralesAJ , ForeroDA. MTHFR gene methylation is associated with perceived stress in healthy young adults. Psychiatr. Genet.28(3), 41–46 (2018).
   PubMed Web of Science ®Google Scholar
• Vaissière T , HungRJ , ZaridzeDet al. Quantitative analysis of DNA methylation profiles in lung cancer identifies aberrant DNA methylation of specific genes and its association with gender and cancer risk factors. Cancer Res.69(1), 243–252 (2009).
   PubMed Web of Science ®Google Scholar
• Barker ED , WaltonE , CecilCAMet al. A methylome-wide association study of trajectories of oppositional defiant behaviors and biological overlap with attention deficit hyperactivity disorder. Child Dev.89(5), 1839–1855 (2018).
   PubMed Web of Science ®Google Scholar
• Walton E , PingaultJB , CecilCAet al. Epigenetic profiling of ADHD symptoms trajectories: a prospective, methylome-wide study. Mol. Psychiatry22(2), 250–256 (2017).
   PubMed Web of Science ®Google Scholar
• Nardone S , SamsDS , ReuveniEet al. DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways. Transl. Psychiatry4, e433 (2014).
   PubMed Web of Science ®Google Scholar
• Wockner LF , NobleEP , LawfordBRet al. Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients. Transl. Psychiatry.4, e339 (2014).
   PubMed Web of Science ®Google Scholar
• Pilsner JR , HuH , WrightROet al. Maternal MTHFR genotype and haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico city. Am. J. Clin. Nutr.92, 226–234 (2010).
   PubMed Web of Science ®Google Scholar
• Liu X , SolehdinF , CohenILet al. Population- and family-based studies associate the MTHFR gene with idiopathic autism in simplex families. J. Autism Dev. Disord.41(7), 938–944 (2011).
   PubMed Web of Science ®Google Scholar
• Bagley PJ , SelhubJ. A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc. Natl Acad. Sci. USA95, 13217–13220 (1998).
   PubMed Web of Science ®Google Scholar
• Antony AC . In utero physiology: role of folic acid in nutrient delivery and fetal development. Am. J. Clin. Nutr.85, S598–S603 (2007).
   PubMed Web of Science ®Google Scholar
• Griffiths R . The Griffiths mental development scales from birth to 2 years, manual, the 1996 revision. Henley: Association for Research in Infant and Child Development, Test Agency (1996).
   Google Scholar
• Achenbach TM . Manual for Child Behavior Checklist/4-18 and 1991 Profile.University of Vermont, Department of Psychiatry, VT, USA (1991).
   Google Scholar
• Goyette CH , ConnersCK , UlrichRF. Normative data on revised Conners parent and teacher rating scales. J. Abnorm. Child Psychol.6(2), 221–236 (1978).
   PubMed Web of Science ®Google Scholar
• Tannorella P , StoccoroA , TognoniGet al. Methylation analysis of multiple genes in blood DNA of Alzheimer’s disease and healthy individuals. Neurosci. Lett.600, 143–147 (2015).
   PubMed Web of Science ®Google Scholar
• Poorang S , AbdollahiS , AnvarZet al. The impact of methylenetetrahydrofolate reductase (MTHFR) sperm methylation and variants on semen parameters and the chance of recurrent pregnancy loss in the couple. Clin. Lab.64(7), 1121–1128 (2018).
   PubMed Web of Science ®Google Scholar
• R Core Team , R Development Core Team. R: a language and environment for statistical computing. (2016). www.r-project.org/
   Google Scholar
• Purcell S , NealeB , Todd-BrownKet al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet.81(3), 559–575 (2007).
   PubMed Web of Science ®Google Scholar
• Gupta N , GuptaS , DamaMet al. Strong association of 677 C>T substitution in the MTHFR gene with male infertility: a study on an Indian population and a meta-analysis. PLoS ONE6(7), e22277 (2011).
   PubMed Web of Science ®Google Scholar
• Zhang Y , HeX , XiongXet al. The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes. Prenat. Diagn.39(1), 3–9 (2019).
   PubMed Web of Science ®Google Scholar
• Yoshimi A , AleksicB , KawamuraYet al. Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data. Schizophr. Res.124(1–3), 216–222 (2010).
   PubMed Web of Science ®Google Scholar
• Stoccoro A , SicilianoG , MiglioreL , CoppedèF. Decreased methylation of the mitochondrial D-loop region in late-onset Alzheimer’s disease. J. Alzheimers Dis.59(2), 559–564 (2017).
   PubMed Web of Science ®Google Scholar
• Lewis SJ , ZammitS , GunnellD , SmithGD. A meta-analysis of the MTHFR C677T polymorphism and schizophrenia risk. Am. J. Med. Genet. B Neuropsychiatr. Genet.135B(1), 2–4 (2005).
   PubMed Web of Science ®Google Scholar
• Muntjewerff JW , HoogendoornML , KahnRSet al. Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype and the risk for schizophrenia: a Dutch population based case-control study. Am. J. Med. Genet. B Neuropsychiatr. Genet.135B(1), 69–72 (2005).
   PubMed Web of Science ®Google Scholar
• Gokcen C , KocakN , PekgorA. Methylenetetrahydrofolate reductase gene polymorphisms in children with attention-deficit/hyperactivity disorder. Int. J. Med. Sci.8(7), 523–528 (2011).
   PubMed Web of Science ®Google Scholar
• Ergul E , SazciA , KaraI. Methylenetetrahydrofolate reductase gene polymorphisms in Turkish children with attention-deficit/hyperactivity disorder. Genet. Test Mol. Biomarkers16(1), 67–69 (2012).
   PubMed Web of Science ®Google Scholar
• Saha T , DuttaS , RajammaU , SinhaS , MukhopadhyayK. A pilot study on the contribution of folate gene variants in the cognitive function of ADHD probands. Neurochem. Res.39(11), 2058–2067 (2014).
   PubMed Web of Science ®Google Scholar
• Schmidt RJ , HansenRL , HartialaJet al. Prenatal vitamins, one-carbon metabolism gene variants and risk for autism. Epidemiology22(4), 476–485 (2011).
   PubMed Web of Science ®Google Scholar
• Coppedè F , DenaroM , TannorellaP , MiglioreL. Increased MTHFR promoter methylation in mothers of Down syndrome individuals. Mutat. Res.787, 1–6 (2016).
   PubMed Web of Science ®Google Scholar
• Saraswathy KN , KaurL , TalwarSet al. Methylenetetrahydrofolate reductase gene-specific methylation and recurrent miscarriages: a case–control study from North India. J. Hum. Reprod. Sci.11, 142–147 (2018).
   PubMedGoogle Scholar
• Grossi E , StoccoroA , TannorellaP , MiglioreL , CoppedèF. Artificial neural networks link one-carbon metabolism to gene-promoter methylation in Alzheimer’s disease. J. Alzheimers Dis.53(4), 1517–1522 (2016).
   PubMed Web of Science ®Google Scholar
• Wei LK , SutherlandH , AuAet al. A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke. Biomed. Res. Int.2015, 167976 (2015).
   PubMed Web of Science ®Google Scholar
• Coppedè F , StoccoroA , TannorellaP , GalloR , NicolìV , MiglioreL. Association of polymorphisms in genes involved in one-carbon metabolism with MTHFR methylation levels. Int. J. Mol. Sci.20(15), pii: E3754 (2019).
   Web of Science ®Google Scholar
• He W , LuM , LiG , SunZ , LiuD , GuL. Methylene tetrahydrofolate reductase (MTHFR) rs868014 polymorphism regulated by miR-1203 associates with risk and short-term outcome of ischemic stroke. Cell Physiol. Biochem.41, 701–710 (2017).
   PubMedGoogle Scholar
• Liu X , WangL , ChiHet al. The SNP rs915014 in MTHFR regulated by miRNA associates with atherosclerosis. Cell Physiol. Biochem.45, 1149–1155 (2018).
   PubMedGoogle Scholar
• Aydin SU , KabukcuBasay B , CetinGO , GungorAydin A , TepeliE. Altered microRNA 5692b and microRNA let-7d expression levels in children and adolescents with attention deficit hyperactivity disorder. J. Psychiatr. Res.115, 158–164 (2019).
   PubMed Web of Science ®Google Scholar
• de Jong S , NewhouseSJ , PatelHet al. Immune signatures and disorder-specific patterns in across-disorder gene expression analysis. Br. J. Psychiatry209(3), 202–208 (2016).
   PubMed Web of Science ®Google Scholar
• Wilmot B , FryR , SmeesterL , MusserED , MillJ , NiggJT. Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2. J. Child Psychol. Psychiatry57(2), 152–160 (2016).
   PubMed Web of Science ®Google Scholar