title: Altered LINE-1 Methylation in Mothers of Children with Down Syndrome.
abstract: Down syndrome (DS, also known as trisomy 21) most often results from chromosomal nondisjunction during oogenesis. Numerous studies sustain a causal link between global DNA hypomethylation and genetic instability. It has been suggested that DNA hypomethylation might affect the structure and dynamics of chromatin regions that are critical for chromosome stability and segregation, thus favouring chromosomal nondisjunction during meiosis. Maternal global DNA hypomethylation has not yet been analyzed as a potential risk factor for chromosome 21 nondisjunction. This study aimed to asses the risk for DS in association with maternal global DNA methylation and the impact of endogenous and exogenous factors that reportedly influence DNA methylation status. Global DNA methylation was analyzed in peripheral blood lymphocytes by quantifying LINE-1 methylation using the MethyLight method. Levels of global DNA methylation were significantly lower among mothers of children with maternally derived trisomy 21 than among control mothers (P = 0.000). The combination of MTHFR C677T genotype and diet significantly influenced global DNA methylation (R2 = 4.5%, P = 0.046). The lowest values of global DNA methylation were observed in mothers with MTHFR 677 CT+TT genotype and low dietary folate. Although our findings revealed an association between maternal global DNA hypomethylation and trisomy 21 of maternal origin, further progress and final conclusions regarding the role of global DNA methylation and the occurrence of trisomy 21 are facing major challenges.
authors.affiliation: Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Ivana Babić
authors.initials: IB
authors.lastname: Božović
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stanković
authors.affiliation: Vinča Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Živković
authors.affiliation: Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Vraneković
authors.affiliation: Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Miljenko
authors.initials: M
authors.lastname: Kapović
authors.affiliation: Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Brajenović-Milić
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000428:Alcohol Drinking / Q000009:adverse effects; D015992:Body Mass Index; D019175:DNA Methylation; D004032:Diet; D004314:Down Syndrome; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009035:Mothers; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
chemical_list: D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)