TY - JOUR
T1 - Differential methylation in APOE (Chr19; Exon Four; from 44,909,188 to 44,909,373/hg38) and increased apolipoprotein E plasma levels in subjects with mild cognitive impairment
AU - Mancera-Páez, Oscar
AU - Estrada-Orozco, Kelly
AU - Mahecha, María Fernanda
AU - Cruz, Francy
AU - Bonilla-Vargas, Kely
AU - Sandoval, Nicolás
AU - Guerrero, Esneyder
AU - Salcedo-Tacuma, David
AU - Melgarejo, Jesús D.
AU - Vega, Edwin
AU - Ortega-Rojas, Jenny
AU - Roman, Gustavo C.
AU - Pardo-Turriago, Rodrigo
AU - Arboleda, Humberto
N1 - Funding Information:
Acknowledgments: Mancera-Páez acknowledges the mentorship of Gustavo Román for this work. Mancera-Páez also acknowledges David Cabello for his support of the neurology education program at Houston Methodist Hospital. We thank Juan Camilo Vargas for methodological advice. Jesus Melgarejo acknowledges the support of the International Brain Research Organization (IBRO) for his research fellowship at the National University of Colombia’s Institute of Genetics through IBRO’s Latin America Regional Committee (LARC) short research training grant between July and December 2018. The authors would like to thank Colciencias for constant support to clinical research in Colombia.
Funding Information:
This work was supported by Colciencias (Code: 110171149904), grant agreement No. 848-2015 and by the Faculty of Medicine National University of Colombia, grant agreement No. 33350. Acknowledgments: Mancera-Páez acknowledges the mentorship of Gustavo Román for this work. Mancera-Páez also acknowledges David Cabello for his support of the neurology education program at Houston Methodist Hospital. We thank Juan Camilo Vargas for methodological advice. Jesus Melgarejo acknowledges the support of the International Brain Research Organization (IBRO) for his research fellowship at the National University of Colombia’s Institute of Genetics through IBRO’s Latin America Regional Committee (LARC) short research training grant between July and December 2018. The authors would like to thank Colciencias for constant support to clinical research in Colombia.
Funding Information:
Funding: This work was supported by Colciencias (Code: 110171149904), grant agreement No. 848-2015 and by the Faculty of Medicine National University of Colombia, grant agreement No. 33350.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/3/2
Y1 - 2019/3/2
N2 - BACKGROUND: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the
APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls.
METHODS: In total, 100 participants were included (71% women; average age, 70 years; range, 43⁻91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and
APOE methylation.
RESULTS: MCI was diagnosed in 41 subjects (average age, 66.5 ± 9.6 years) and compared with 59 controls. Elevated plasma ApoE and
APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (
p < 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (
p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = -0.665;
p = 0.008).
CONCLUSION: Differential
APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI.
AB - BACKGROUND: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the
APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls.
METHODS: In total, 100 participants were included (71% women; average age, 70 years; range, 43⁻91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and
APOE methylation.
RESULTS: MCI was diagnosed in 41 subjects (average age, 66.5 ± 9.6 years) and compared with 59 controls. Elevated plasma ApoE and
APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (
p < 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (
p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = -0.665;
p = 0.008).
CONCLUSION: Differential
APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI.
KW - APOE gene
KW - Apolipoprotein E
KW - DNA methylation
KW - Hispanics
KW - Mild cognitive impairment
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U2 - 10.3390/ijms20061394
DO - 10.3390/ijms20061394
M3 - Article
C2 - 30897703
AN - SCOPUS:85063670911
SN - 1661-6596
VL - 20
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 6
M1 - 1394
ER -