AM L4 Risk

Question 1

How do population studies help us see genetic link?

Answer 1

If a population have a greater risk look at the particular genes in the populaiton

Question 2

3 proposed genetic targes

Answer 2

Toll receptors
Inflammatory mediators
Homocysteine

Question 3

How many genes are thought to influence predisposition to ATS?

Answer 3

400

Question 4

2 reasons genetic studies are difficult for ATS?

Answer 4

heterogeneity of the population

complexity of a polygenic multifactorial disease

Question 5

Non-modifiable risk factors (12)

Answer 5

MI
Stroke
Total chol
HDL
Total triglycerides
BMI
Systolic BP
Homocysteine levels
T2DM
Fibrinogen
C-reactive component
Gender

Question 6

What is a polymorphism?

Answer 6

a common genetic variation, affecting at least 1% of the population - results in different phenotypes

Question 7

2 examples of different phenotypes

Answer 7

Blood groups

Major histocompatibility complex

Question 8

Population studies show results if (3)

• we must consider all these options

Answer 8

True increase in susceptibility
Allele closely linked to real allele of pathogenesis
Coincidental

Question 9

Population migration, where in the world has high risk and where low of CAD?

Answer 9

Japan has low risk compared to USA
BUT
Japanese-american = other americans

so is this genetic or environmental?

Question 10

2 Monogenetic disorders that revolutionised understanding?

Answer 10

Tangiers disease

Familial hypercholesterolemia

Question 11

Tangiers disease is a genetic disorder of….

Answer 11

cholesterol transport

Question 12

Which gene is mutated in Tangiers?

on which chromosome?

Answer 12

ABCA1 gene mutation in chromosome 9q31

Question 13

Tangiers disease results in mutant ………. and therefore reduced….

Answer 13

mutant ACBA1 transporter = reduced ability to transport chol out of cells. Cholesterol accumulates in the cell

Question 14

Chol combines with …. to form HDL

Answer 14

apoA1

Question 15

Tangiers disease results in reduced circulating

Answer 15

HDL

Question 16

Tangiers provided the theory that….

Answer 16

low HDL increases CVD

Question 17

HDL can pick up more lipids from ……… & ….. and take them …..

Answer 17

VLDL and LDL

back to the liver

Question 18

What happens to ApoA1 lipoprotein in Tangiers?

Answer 18

it is cleared from the plasma

Question 19

Conditions associated with Tangiers

Answer 19

Thrombocytopenia
corneal opacity
orange tonsils (build-up of cholesterol droplets)
premature MI

Question 20

Familial Hypercholesterolemia is a loss of function of ….. receptor

Answer 20

LDL receptor (absent or deficient)

Question 21

Familial Hypercholesterolemia results in decreased…..

Answer 21

LDL uptake by the liver

Question 22

How does Familial Hypercholesterolemia clinically manifest?

Answer 22

elevated plasma LDL

Question 23

What happens to the cholesterol in Familial Hypercholesterolemia?

Answer 23

deposited in tissues, forms nodules.

Question 24

What are nodules of cholesterol called?

Answer 24

Xanthoma

Question 25

Where do chole nodules appear in Familial Hypercholesterolemia? (2)

Answer 25

Skin and tendons

Question 26

If someone is homozygous for Familial Hypercholesterolemia what happens?

Answer 26

death from CHD in childhood

Question 27

What is the only treatment for Familial Hypercholesterolemia?

Answer 27

Liver transpolant

Question 28

What happens to people who are heterozygous for Familial Hypercholesterolemia?

Answer 28

Milder more variable course of disease

Question 29

What proportion of people are heterozygous for Familial Hypercholesterolemia

Answer 29

1 in 500