Jessica Burdo, Howard Steiger, Lea Thaler, Esther Kahan
Title of Presentation:
Correspondences between Plasma Nutrient Levels and DNA Methylation Patterns in Individuals with Anorexia Nervosa
Name of Institution:
McGill (Conducted at the Eating Disorders Continuum at the Douglas Mental Health University Institute)
Recent findings suggest that people with Anorexia Nervosa (AN) display altered DNA methylation, an epigenetic mechanism postulated to have etiological significance. Methylation is responsive to nutritional factors, and thus implies that nutritional deficits in people with AN may contribute to anomalous methylation patterns. We examined the relationships between global and site-specific methylation levels, and plasma levels of micronutrients involved in the methylation pathway in three groups: AN-Active (n=42), AN-Remitted (n=32) and no eating disorder (NED: n=30). Preliminary analyses suggested that, relative to NED controls, AN-Active people had higher levels of B12 (p=.01) and betaine (p=.02), and AN-Remitted participants had higher levels of B12 (p=.03). We further found that methionine levels were negatively correlated with global methylation; a finding that held for AN-Remitted (r=-.50, p=.02) and NED participants (r=-.47, p= .04) when analyzed separately, but not for AN-Active participants. This relationship may again be attributable to choline influx in blood cells that enables methylation despite the lack of dietary micronutrients. Our preliminary results suggest that people with AN show elevations on some nutrient levels--increases that are paradoxical given their state of malnutrition, but which we speculate may be attributable to choline mobilization from tissue to blood cells. Analyses now-underway examine group-based effects on probe-specific methylation levels, and will help clarify the relationships between micronutrients and methylation levels in AN.
Innovative Technique Employed:
The research proposed analyzes DNA methylation (or the amount of methyl bound to CpG sites in the genome) whose high or low quantities silences or enhances genetic expression respectively. Methylation is an epigenetics process: a new science that investigates how environmental stressors modify genetic expression on a molecular level. Implications of such research are a better understanding of etiology, and developing novel treatments to improve pathology. Methylation is measured using cutting-edge technology: the high throughput Illumina Infinium BeadChip that now analyzes over 850k sites at single nucleotide resolution. Signals from the chip are read with a scanner that quantifies site-specific methylation levels for an individual. Furthermore, we implore mass spectrometry and the ELISA Kit to measure levels of micronutrients that affect methylation. Results are integrated and analyses are done using the Minfi Package in R which enables sophisticated statistical analyses for massive amounts of data such that of our study.