Week 3: Cardiovascular genetics

Question 1

Discuss the current state of genetic risk prediction of common cardiovascular diseases based on SNP genotypes.

Answer 1

• magnitude of common genetic risk factors is relatively small for CV diseases
• genetic risk prediction is at an early stage and insufficient evidence exists at present to warrant the use of genetic risk scores based on SNP genotypes

Question 2

Recall Federal law that prohibits discrimination in health coverage and employment based on genetic information

Answer 2

• GINA genetic information nondiscrimination act of 2008

- employers can’t fire, refuse to hire, or other workplace discriminations based on genetic information

Question 3

Discuss how APOC3 mutation status illustrates the role human genetics can play in validating therapeutic targets for cardiovascular disease

Answer 3

• APOC3 inhibits lipoprotein lipase and hepatic lipase, thought to delay catabolism of TG rich particles
• decreasing APOC3 should increase TG catabolism and reduce levels in plasma
• studies have found individuals who are heterozygous for APOC3 mutations that inactivate gene function have reduced levels of non fasting TGs and reduced levels of ischemic vascular and ischemic heart disease
• APOC3 is a relevant drug target for reducing residual CV risk

Question 4

Debate the relative merits of genetic testing for clopidogrel treatment decisions.

Answer 4

• common CYP2C ‘loss of function’ SNP only explains 12% of the variation in platelet response in patients
• unknown factors explain >70% of the variation
• FDA recommends testing but another study doesn’t recommend it until clinical trial shows it is beneficial