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Printable Handouts
Navigable Slide Index
- Introduction
- Agenda
- What are risk factors for heart disease?
- Healthy artery
- Endothelial dysfunction & early fatty streaks
- Advanced lesions
- Complicated and unstable plaque
- Atherosclerotic plaques – human post-mortem
- Advanced lesions and plaque rupture
- Atherosclerosis in arteries in the heart
- Atherosclerosis progression
- Atherosclerosis progression – candidate genes
- The molecular genetics of CHD
- Heart disease risk is multifactorial
- How do we choose the genes to study?
- What is a SNP?
- Study design
- Plasma lipoprotein metabolism
- Structure and components of lipoprotein particle
- Why is LDL atherogenic?
- Plenty of candidate genes from lipid metabolism
- Monogenic disorders of lipid metabolism
- Cant do all experiments in human subjects
- Mouse as a good animal model of atherosclerosis
- But - different lipid profile in humans/mice
- Atherosclerosis in aortic root after 18 weeks diet
- Animal models of atherosclerosis
- So how do we carry out candidate gene studies?
- Meta-analysis of TG and CHD risk
- Identification of APOA5
- Proposed mechanism of action of ApoA5
- Northwick Park Heart Study II
- Human studies: APOA5 SNPs and TG levels
- Meta-analysis of -113T>C and TG and CHD
- APOA5 -1131T>C and CHD
- Candidate gene studies – steps in pathway
- APOA5 SNPS and haplotypes
- Luciferase assay
- Functional studies on APOA5 SNPs with TG levels (1)
- Functional studies on APOA5 SNPs with TG levels (2)
- Mechanism of action of ApoAV
- Candidate gene SNP chips
- 50k illumina human cardio-metabolic chip
- Study sample
- Analytical strategy
- Manhattan plots for TG
- Percentage of variance explained
- Clinical utility of lowering TG concentration
- Novel candidate genes and novel treatment targets
- APOC3 antisense
- Summary 1: role of genes
- Summary 2: missing heritability
- Candidate gene approach
Topics Covered
- The causes and mechanisms of heart disease
- Plasma lipid metabolism
- Identification of candidate gene
- Relevant animal models
- Human studies
- Proving functionality of candidate SNPs
- APOA5 SNP studies
- Phenome scans using candidate SNP chips
- Novel anti-sense approaches for lipid-lowering
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Humphries, S. (2024, March 31). Heart disease genes and SNPs [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 14, 2024, from https://doi.org/10.69645/BDQF1468.Export Citation (RIS)
Publication History
Financial Disclosures
- Professor Humphries is the Medical Director of StoreGene a UCL spin out company that offers DNA testing for Cardiovascular Disease risk including testing for FH. Professor Humphries is a consultant for Verve Therapeutics, a US based company that is developing gene-editing agents to treat individuals with hypercholesterolaemia, including those with FH.
A selection of talks on Genetics & Epigenetics
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Steve Humphries.
I'm the Emeritus British
Heart Foundation Professor of
Cardiovascular Genetics at
University College in London.
I'm going to talk today
about heart disease genes,
and single nucleotide
polymorphisms or SNPs.
0:20
The outline of the
talk is shown here.
0:25
I want to start by
discussing what
are the common risk
factors for heart disease.
Now, you probably
can all name these,
but here is a list
of what I think are the
most important ones.
Age and male gender are by
far the largest factors.
Smoking, obesity,
having high blood
pressure, being diabetic.
Then we get down to
things like having a lack
of exercise in your
lifestyle or lots of stress.
Then things we can measure
in the blood is having
high low-density
lipoprotein, or LDL.
In the lay press,
that's called the
bad cholesterol,
or low high-density
lipoprotein, that's HDL.
In the lay press that's
called the good cholesterol.
Now when you look
at these factors,
you can see that
some are modifiable.
You can obviously change
whether you're smoking.
You can maybe lose weight.
You can start taking
more exercise.
Some are purely genetic.
Clearly you can't do
anything about your gender.
Then some are a bit of both.
In other words, you
could say, well,
I'm smoking because
I've got a bad genes,
but clearly that's part
of your environment.
The same thing with some of
the other factors there.
When we're thinking about
what's causing heart disease,
we've got to consider both
genes and the environment.
Let's talk now about what are
the processes of heart disease.
In some of the slides, I'll call
this CHD or coronary
heart disease.