AM L4 Risk Flashcards
How do population studies help us see genetic link?
If a population have a greater risk look at the particular genes in the populaiton
3 proposed genetic targes
Toll receptors
Inflammatory mediators
Homocysteine
How many genes are thought to influence predisposition to ATS?
400
2 reasons genetic studies are difficult for ATS?
heterogeneity of the population
complexity of a polygenic multifactorial disease
Non-modifiable risk factors (12)
MI Stroke Total chol HDL Total triglycerides BMI Systolic BP Homocysteine levels T2DM Fibrinogen C-reactive component Gender
What is a polymorphism?
a common genetic variation, affecting at least 1% of the population - results in different phenotypes
2 examples of different phenotypes
Blood groups
Major histocompatibility complex
Population studies show results if (3)
- we must consider all these options
True increase in susceptibility
Allele closely linked to real allele of pathogenesis
Coincidental
Population migration, where in the world has high risk and where low of CAD?
Japan has low risk compared to USA
BUT
Japanese-american = other americans
so is this genetic or environmental?
2 Monogenetic disorders that revolutionised understanding?
Tangiers disease
Familial hypercholesterolemia
Tangiers disease is a genetic disorder of….
cholesterol transport
Which gene is mutated in Tangiers?
on which chromosome?
ABCA1 gene mutation in chromosome 9q31
Tangiers disease results in mutant ………. and therefore reduced….
mutant ACBA1 transporter = reduced ability to transport chol out of cells. Cholesterol accumulates in the cell
Chol combines with …. to form HDL
apoA1
Tangiers disease results in reduced circulating
HDL
Tangiers provided the theory that….
low HDL increases CVD
HDL can pick up more lipids from ……… & ….. and take them …..
VLDL and LDL
back to the liver
What happens to ApoA1 lipoprotein in Tangiers?
it is cleared from the plasma
Conditions associated with Tangiers
Thrombocytopenia
corneal opacity
orange tonsils (build-up of cholesterol droplets)
premature MI
Familial Hypercholesterolemia is a loss of function of ….. receptor
LDL receptor (absent or deficient)
Familial Hypercholesterolemia results in decreased…..
LDL uptake by the liver
How does Familial Hypercholesterolemia clinically manifest?
elevated plasma LDL
What happens to the cholesterol in Familial Hypercholesterolemia?
deposited in tissues, forms nodules.
What are nodules of cholesterol called?
Xanthoma
Where do chole nodules appear in Familial Hypercholesterolemia? (2)
Skin and tendons
If someone is homozygous for Familial Hypercholesterolemia what happens?
death from CHD in childhood
What is the only treatment for Familial Hypercholesterolemia?
Liver transpolant
What happens to people who are heterozygous for Familial Hypercholesterolemia?
Milder more variable course of disease
What proportion of people are heterozygous for Familial Hypercholesterolemia
1 in 500
