title: Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: a cohort study.
abstract: In the last years, epigenetic processes have emerged as a promising area of complex diseases research. DNA methylation measured in Long Interspersed Nucleotide Element 1 (LINE-1) sequences has been considered a surrogate marker for global genome methylation. New findings have suggested the potential involvement of epigenetic mechanisms in Type 2 diabetes (T2DM) as a crucial interface between the effects of genetic predisposition and environmental influences. Our study evaluated whether global DNA methylation predicted increased risk from T2DM or other carbohydrate metabolism disorders in a cohort study. We used a prospective cohort intervention study and a control group. We collected phenotypic, anthropometric, biochemical, and nutritional information from all subjects. Global LINE-1 DNA methylation was quantified by pyrosequencing technology. Subjects that did not improve their carbohydrate metabolism status showed lower levels of global LINE-1 DNA methylation (63.9 ± 1.7 vs. 64.7 ± 2.4) and they practiced less intense physical activity (5.8% vs. 21.5%). Logistic regression analyses showed a significant association between LINE-1 DNA methylation and metabolic status after adjustment for sex, age, BMI, and physical activity. Our study showed that lower LINE-1 DNA methylation levels were associated with a higher risk metabolic status worsening, independent of other classic risk factors. This finding highlights the potential role for epigenetic biomarkers as predictors of T2DM risk or other related metabolic disorders.
authors.affiliation: a UGCI de Endocrinología y Nutrición ; Instituto de Investigación Biomédica de Málaga (IBIMA) ; Hospital Regional Universitario ; Malaga , Spain.
authors.forename: Gracia María
authors.initials: GM
authors.lastname: Martín-Núñez
authors.forename: Elehazara
authors.initials: E
authors.lastname: Rubio-Martín
authors.forename: Rebeca
authors.initials: R
authors.lastname: Cabrera-Mulero
authors.forename: Gemma
authors.initials: G
authors.lastname: Rojo-Martínez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Olveira
authors.forename: Sergio
authors.initials: S
authors.lastname: Valdés
authors.forename: Federico
authors.initials: F
authors.lastname: Soriguer
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Morcillo
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
keywords: BMI, body mass index.; CVD, cardiovascular diseases; DNA methylation; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; LINE-1; LINE-1, Long Interspersed Nucleotide Element 1; T2DM, Type 2 diabetes mellitus; cohort study; diabetes; peripheral blood cell