17. Genomics and epigenetics in public health. Nutrigenomics

From greek.doctor
  • Most diseases with a genetic component can not be traced back to a single gene but rather multiple
    • Exceptions: Cystic fibrosis, Huntington disease
  • Genomics = the interactions of all genes and their combined influence on the organism
    • Genetics = the study of heredity. The effect of single gene mutations on the organism
  • Genomics in public health – Using genome-based discoveries for health benefits of the population
  • Genomics are important in
    • Determining why exposure only causes the disease in some people
    • Determining why prognostic factors have different importance in different people
    • Determining why treatment only works in some people
  • How to start:
    • Candidate gene studies
      • A gene is suspected for having a role in disease
      • Identify differences in one gene in patients and controls
    • Genome-wide association studies
      • No prior gene candidate is needed
      • Identify genetic differences in the whole genome of patients and controls
      • Can find alleles of a gene which increases susceptibility
  • Personalized medicine
    • Use genetic testing to find screening, treatment, and other preventative measures that are best suited for the patient
    • Will prevent overdiagnosis and overtreatment
    • Examples
      • Genetic information of nicotine metabolism can be used to personalize smoking cessation
      • Genetic information can give indication for screening, if high-risk genotypes are present
      • Genetic information can tell us upfront which treatments will be most effective

Epigenetics

  • Definition: Instructions for the cell on how and when to read DNA
  • Epigenetics changes gene expression
  • Genetically identical organisms can have different phenotype due to different epigenetics
  • Types
    • Acetylation of histones
    • Methylation of DNA
    • Presence of miRNA
    • Chromatin remodelling
  • Environmental factors can change epigenetics of an individual, and therefore the expression of the DNA
  • Folic acid necessary for DNA methylation -> deficiency could theoretically cause hypomethylation and carcinogenesis
  • MicroRNA profiles in blood could be used as biomarkers
    • Already used for CRC
  • Drugs affecting epigenetics = epigenetic drugs
    • Used as chemotherapeutic agents against cancer
    • Epigenetic alterations are reversible and can be reversed by these drugs
      • Unlike genetic mutations
    • They demethylate DNA or acetylate histones
      • This can reactivate silenced tumor suppressors, repress activated oncogenes, etc.

Nutrigenomics

  • Definition: The relationship between nutrition and genomics
    • Basically how what you eat can change epigenetics
  • Deficiency of certain nutrients (folate, B12, C, E) can cause DNA changes similar to those seen after radiation
  • Folate
    • Folate is required for DNA methylation
    • Folate deficiency -> DNA hypomethylation -> carcinogenesis
  • Methyl-donating nutrients
    • Diets high in methyl-donating nutrients can alter gene expression
    • Especially during early development
    • Examples
      • Methionine
      • Folate
      • B12
  • Maternal nutrition
    • Maternal nutritional status during early pregnancy can cause permanent epigenetic changes in the foetus