Genetic Risk and Altering Lipids With Lifestyle Changes and Metformin

Nutriepigenomics Advances into Personalized Nutrition

“…Diseases interrogated with well-powered GWAS demonstrate that the majority of risk alleles reside in noncoding regions and have small effect sizes and would not achieve genome-wide significance in more moderately sized cohorts [2,6]. Therefore, methods to provide biological validity to both supra-and sub-threshold variants are a high priority.…”

“…Studies focusing on the developmental origin of health and disease have identified links between early nutrition and disease, consistent with the "developmental origins of health and disease" (DOHaD) hypothesis. This hypothesis postulates that early life development is critically sensitive to inadequate nutrition and other environmental factors, leading to permanent changes or marks in development that can influence the health of an individual in later life and increase their risk of disease [2,6,7,8].…”

“…The impact of nutrition on genomic DNA methylation through one-carbon metabolism is well-documented. Specifically, it has been demonstrated that dietary deficiency or excess of the methyl group donors needed for the cellular methylation reactions can alter epigenetic patterns, which may persist for a long period and alter gene expression causing phenotypic changes [6]. The vitamins choline, folate, B6 and B12 are cofactors essential to maintaining the one-carbon transfer cycles [1,8,9].…”

“…Dietary components (amino acids, high-fat or high-glucose diet, vitamins, bioactive factors,) can affect genome function and gene expression in utero and during early life, influencing epigenetic mechanisms through folate-mediated one-carbon metabolism or transmethylation pathways to affect DNA methylation, histone, or non-coding miRNAs [6]. In contrast, the impact of diet on other epigenetic mechanisms, including histone modification, chromatin modifying proteins, and microRNA (miRNA) expression is poorly defined.…”

“…The epigenetic state that is set during the reprogramming stages persists at some loci for the lifetime of an individual. Evidence to support a role of epigenetics in developmental programming of disease demonstrated the impact of a suboptimal intrauterine nutritional environment on the epigenome and phenotype of the offspring [1][2][3][4][5][6].…”