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A study of normalization methods of 450K methylation microarray and association of a FTO gene variant and exercises with epigenetic changes by modeling Open Access

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Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. Variants of the FTO gene show strong association with obesity, but the mechanisms behind this association remain unclear. We also investigate the mechanisms behind the association of exercise and FTO gene with obesity. We determined the genome wide DNA methylation profile in muscle from 31 subjects. We identified sites associated with the genes PLEC, Id1, ISL1 and PAX7 that had a significant differential methylation level in the carriers of the FTO risk allele (rs9939609). Our finding agrees with the previous discovery that FTO encodes an m6A demethylase and implicates m6A as an important regulator of physiological processes.Our findings suggest that the effect of the FTO obesity risk allele may be mediated through epigenetic changes. The networks generated showed an improvement in muscular development, endurance and metabolism following the intervention. Although it should be noted that it is a hypothetical model and would need further validation using methods like pyrosequencing and/or functional assays.

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