Anorexia contemporary - SVZ

• What was the purpose of the SVZ study?

  To identify genes involved in AN development
• What type of DNA samples were used in the SVZ study?

  DNA from 25 females with severe AN
• What was the mean age of onset for the females with AN in the study?

  14 years
• How many control females were included in the SVZ study?

  73 control females
• Which scales were used to record scores in the study?

  Beck's depression inventory and others
• How many candidate genes were identified as involved with AN?

  152 candidate genes
• What biological mechanisms were linked to the candidate genes?

  Feeding behavior, dopamine, and serotonin function
• How many AN samples were used to confirm the genes linked to AN?

  50 AN samples
• What was the mean onset age for the AN samples used in confirmation?

  15 years
• How many non-sufferer's DNA samples were taken for comparison?

  500 non-sufferer's DNA samples
• What was the source of the DNA samples used in the study?

  Price Foundation sample repository
• How did the second sample of DNA contribute to the study?

  It confirmed the genes being investigated
• What gene was found to be worth further investigation in the initial sequencing of the CNA?

  EPHXZ (EpOxide Hydrolase 2)
• What did the next phase of testing indicate about the EPHXZ gene?

  It showed the greatest variation between the AN cases and the control samples
• What were the characteristics of the AN cases with the variant EPHXZ gene?

  They demonstrated the highest scores on measures of depression and the lowest BMI scores
• How many additional AN cases and controls were assessed when the association between EPHX2 and AN was found?

  500 additional AN cases and 500 controls
• How does the EPHX2 gene influence cholesterol metabolism in AN patients?

  AN patients with the variant EPHX2 gene often have high cholesterol even though they are malnourished
• In which areas of the brain is the EPHX2 gene expressed?

  The paraventricular nucleus of the thalamus, which is associated with food/water intake and the body's stress response
• What was found in the Bogalusa Heart study regarding the EPHX2 gene and AN?

  Similar results were found, with 386 AN cases (female and male) showing differences compared to 295 female controls
• What other gene was found to be connected with the development of AN?

  ESR2
• Why does the evidence for the ESR2 gene variant suggest that estrogen and estrogen receptors may have a role in mediating AN?

  Because AN is observed in female subjects to a much higher degree than in male subjects, and typically has onset in adolescence
• What is the overall conclusion from the evidence presented?

  The evidence suggests that the variant of the EPHX2 gene may increase the risk of developing AN and shows that further research is needed in biological causes of AN
• What were the key findings from the initial sequencing of the CNA?

  • The gene EPHXZ (EpOxide Hydrolase 2) was found to be worth further investigation
  • This gene showed the greatest variation between the AN cases and the control samples
• What is the relationship between the EPHX2 gene, cholesterol metabolism, and AN?

  • The EPHX2 gene influences cholesterol metabolism
  • AN patients with the variant EPHX2 gene often have high cholesterol even though they are malnourished
  • This provides further support for the involvement of the EPHX2 gene in AN
• What is the evidence for the role of estrogen and estrogen receptors in AN?

  • Variants of the ESR2 gene were found to be connected with the development of AN
  • AN is observed in female subjects to a much higher degree than in male subjects
  • AN typically has onset in adolescence, suggesting estrogen and estrogen receptors may have a role in mediating the disease
• How did the findings from the Bogalusa Heart study support the association between EPHX2 and AN?

  • The Bogalusa Heart study found similar results, with 386 AN cases (female and male) showing differences compared to 295 female controls