09.

48

It's from the traditional medicine with the one-size-fit-all therapy, which is everybody would get the
same therapy for the same disease. But now, with a funny advancement in the genomic medicine, either
switch to the Precision medicine, where the therapy were based on the genomic background on the
each individual's, and the genomic variants will direct us to the natural course of the disease, which can
lead us. Us. See the more personalized treatment sector including the verbal therapy. It can also be
personalized. Not only the work on ecology, but also the risk of developing more severe disease, the
protease and also in here, Precision medicine, not only covered from the pharmacology downside but
also to the other for example for the exercise correctly exercise, Right, exercise for the people and also
the nutrients Etc.

So, in terms of cardiovascular disease, a genetic background of, canoe paddler disease, can be consists
of two types, which is the cardiac disease which with single family and cows.

Disease. 35. 36, which inherited in mentally and manner such as the hypertrophic kind of value. My Petit
dilated cardiomyopathy,

Also, the Long QT syndrome and - heart disease, but there are the type of cardiovascular disease, which
caused by multiple variants in different genes and this is this is not generated image in million manner.
But it's not non-mendelian. In this case, cardiovascular disease could be caused by several genes acting
all together because the phenotypes. But in this presentation, I would like to focus on cardiovascular
disease with single variance in a single variance in single genes, but only few of other or talk about For
the phenotype which is, you know, that basis, we can see for the phenotype which is, you know, the
basic of the genetic do, cardiovascular can direct us to the more precise diagnosis and we can risk -
therapy and also risk dressed as The reproductive decisions for the patient has. And I hear the
monogenic, or inheritance in energetic cardiovascular disease, inherit is Porter, aware of rare genetic
variation but usually it has the large effect. Large effect recording. High penetrance, while the polygenic,
disease, the variants might cause only a small effect, and then here, there's such a chance also for their
Gene environment interaction in between, there is a halogen or inheritance a rare genetic with a
moderate effect. And the most of cardiovascular disease with single quotes or single mutation in a single
Gene edited in awe. So small domain and memory, most of them. But also the autosomal recessive and
expectant might also be also

So, here are the sum of the inheritor cardiovascular disease and in this is the most Petty, Facebook
integrated cardiovascular disease consists of cardio. My parties are eating disorders. Butter actually,
cortical isms in the sections. and also, I would like to talk about a little about the cardiovascular
mortality, which is the part of genetic syndromes for example, students in rural or the recipe Hold on. In
those cases in those.

Genetic testing is needed to confirm the diagnosis and later, we just the management as appropriate to,
this is what we call the Precision medicine. Looking into the genetic background to see the nature of the
disease and then adjust appropriate, most appropriate management for its patients.

And I should note here that the genetic testing might not, do you feel the course of confirm the
diagnosis? Well here, because that might be, we might found some variants with. We don't know what,
we're not sure whether the variant is pathogenic or the causative variant for this disease. In this case,
genetic testing might reveal or confirm the diagnosis. So, for the first this is Outlet to talk about it
inherited. Cut your mind fatty and this is the disorder of The myocardium due to genetic defect confused
or hypertrophic cardiomyopathy can also be in form of dilated cardiomyopathy and edit my chain
Academy. Happy Thank you.

This will cause the genotype which is here. Each individual will have genetic backgrounds influence. The
burden of caring. And also in the other side, the might also be individual environment Factor, but in this
Heritage schedule, my fact the effect of the environment factors is not so big as acquired that you my
fatty.

So, if you look at the genes, which caused the third you my fatty diseases, we can see for from this
picture that This is where the cardiac cells and a year, you can see the cell membranes, the sort of also
the title of a different cardiomyocyte and here the location of the genes

Well yeah, in front of course, the phenotype of the cardiomyopathy. Here. And the Capper tropical you
my fatty and edit my genic hydrophilic, cardio, my fatty the genes are usually last part in the sarcomere
so we can see in the central with the genes, which are TMS is one DNA T2 and became one if it is e 1 and
E VG, L NC, ET en mean Mil to and male 3. And also those genes we just in the this muscles, DM am 43,
DSP GST to yes, yes, yes, to ju P & B KP to the chain, is the variant better genetic variants, which is
located in the Polymer, or links discard Colima and extracellular Matrix to see the skeleton that is. Ya SE
n. 580 M DD sf3 bln and and a at the M20 are usually causing the dilated cardiomyopathy. So bye.

Okay. Also genes, we can do before we can see the basic genetics nature of the cutting my party.
To implement Precision medicine in the case of cardiomyopathies? Well, here first that establishing the
clinical diagnosis of cardiomyopathy is the most important thing. The first thing we should do and we
look at the phenotype, I think the clinic, I mean, the clinical features, which are we can pull up the
patient's into whether they have a trophy cardiomyopathy. Tea, or dilated cardiomyopathy or added
more genic, right? Ventricular cardiomyopathy. And then from, there we identify the causative factors
you can see the weather. There is the Jean with a gene mutation makes around genetic variation. And
also we can see whether the patients have comorbidities left are vectors. And also we do the
phenotype, more on the phenotype assessment. Like, for example, we do the electro continue their fee
echocardiogram Coffee or we check for the histological and structure of the Guardian mindset from.
There we can derive this leaks that education and arrange for the British Invasion. Based on the variant
or Gene mechanism based therapy or we can Target it to use of the heart failure or anti-arrhythmic
therapies and also if we detect some risk factors laughter vectors which is already high above risk factors
so not only in terms of overlap College equipments but also modify all modifiable. Instruments. This is
some example or in implementation, personalized medicine in Heritage schedule. My fatty for example,
patients with the variant PR Ragini at 20 220 plus q and s. CN 518 they can be effective in created by
sodium channel. Blocker for example fika in it amiodarone and Canadian Those who

The carriers of sarcomere. Gene mutation might have been earlier onset of disease and high rates of
sudden cardiac death in an apologetic, right? Ventricular cardiomyopathy vacation with pathogenic
dismiss, more variance, right? Had earlier onset disease and ventricular arrhythmia. So this in this
patient's, the threshold for the in ICD implantation earlier than the ICD implantation earlier than do the
ICD implantation earlier than the other side of operations. Here, the exercise prescriptions should also
be individually tailored according to the patient related vectors

Yes, we want to edit mirrors, so most go searching for inherited. Cardiac arrhythmias in got the Cardiff,
giant, Jenga profit. So they are in most of them are inherited in an autosomal dominant manner, the rest
of it can be sort of sensitive or the existing And this is the attic Mia is the major cause of sudden, cardiac
death is the example of inherited. That is Mia or the Long QT syndrome molecule DS DS brugada
syndrome, the catecholamine energy, polymorphic ventricular tachycardia. And the family a atrial
fibrillation the prolonged QT syndrome usually patients. We will have increased risk of syncope and
sudden cardiac death and the L QT s consists of some pipes to help you QT 1 and Q 2 and Q 3, which is
eat had half.

For example, the lqt one is declared by emotional distress of physical activity activity to usually patients
will be
Period and postpartum period and the LG G3. Most common happened during sleep or grass.

Right side, genius that contribute to the event, over the a Long QT syndrome For example, the ACN q1,
the potassium Channel, Gene, Jesse and X2 sodium as cn5 a poor country and the those are definitive
evidence with

F QT s and the F QT s. And the F QT s, and the next trip is those genes which has strong or moderate
ophidians like CAC and A1C. What the FBI and some other genes are have limited or disputed evidence
for the LeapPad qds. Us. So, in here, the location and the type of rotation for example, whether the
mutation is missense frames force, or splice site will affect the degree of time. ION channel dysfunction,
and pain, phenotypic infestation, for example, young patient, that affect the transmembrane a little
more severe and crawfish alleged proper phenotypes, the space station with those patients tend to
manifest in

Effects. So for some quotations, which should wear that the weeks or adverse cardiac effects. So for
some quotations, which should wear that patients might have a worse prognosis,

So, this is the example of the genotype guided risk stratification, and management of the

We can have the how to grip the main investor patients like for example, for love you think one by one
with a mutation on the kg + q1 the patient should avoid emotional physical distress and I in this patient,
the entire genetic therapy. For example, needle will be highly effective so for the Long QT type 2, We
can mutation on K, G and H 2. It's usually should be treated very aggressive monitor or representation
and avoid sudden noise exercise collagen and in these patients, the use of non-selective beta blocker for
example, and let alone is prefer. And then the Long QT, three with the mutation in SE n Pi, a here.

10.05

The use of it.

10.05
Ones are no laws and on selective ones, I prefer to sodium channel. Blocker if the QT interval Falls more
than 500 in second.

Next is, Syndrome. Look at the syndrome is higher is of ventricular, arrhythmias and sudden cardiac
death with the genetic basis is a definitive evidence is a mutation on sem 5A interior in the broken
decision in Roe. So one type 1 type 2 type 3 right here the roller derby testing is as well as established as
those in multiplication. So, this is the illustration, the overview from, The Long QT, syndrome the
brugada syndrome and also have to adhere the familial atrial fibrillation which are attribution can be
caused by metabolic factors. For example, obesity or hyperglycemia because the eternity modeling but
also the if it's familiar then it will inherit

Relation, which we can also get direct and Direction on the current and future president medication.

But IX cardiovascular disease is heritable. Proxy partic. This is, this is there are some terrific out, like
disease, but I would like only talk in detail about Marfan syndrome because this is what I learned during
my master study, what a function G is a connective tissue disorder, which is inherited in an autosomal
autosomal dominant Manner and clinical phenotypes of Marfan syndrome, Long fingers or a tall stature
with long fingers, or a, a technology effectively, and lens dislocation High myopia and also the cardiac
manifestations I usually consists of the out economy. Some intersection it rough or the abnormalities on
cardiac problems. So here the mortality and morbidity mainly caused by the section of or rupture of the
aortic aneurysm and of course of this Marfan syndrome is a genetic variant in the fibula in gene. One of
them component of the connective tissue.

Dribbling one Gene, and there are two types of the effect of variation, dribbling one Gene, and then the
Bavarian can be causing her blow insufficiency which is the amount of the normal connective tissue,
normal fibrillation is, less than sufficient amount but also the variant might work because dominant -
Korean where the ferry and of course, the abnormal form, This disease might cause will depict variability
among family members. So what we do in Marfan syndrome, the current robotics strategy consists of
practicality surgery in the presence of a kind of isms first premium products, ecological Energy Systems,
where the prosthetic of the Far Far replacement and also. To reduce the heart rate and consists of
antihypertensive to reduce the heart rate and blood pressure. And so here at the end, if the purpose of
treatment can reduce decrease, the press, or the pressure on the week aneurysm,
First to do patience with a police official. Invitation are in free space of cardiovascular, death and
authentic dissection. But to patient with dominant-negative mutations. So do you differentiate whether
the patients have a happy insufficiency or domain - is essential here? The surgical approach. Also the

10:00 11:00. Maybe follow em at 10:00 11:00. Maybe follow em At decreasing heart rate, lowering
blood pressure and and your tension receptor blockers. We use the sub button and falser than this and
it ends in acceptable of I have you will go. One is as the end and tie a tail see. Now that is that the ARB
have evap or sewing, The OT, good group 100 patients. So here, the the use of ARB is both beneficial in
terms of reducing hemodynamics press as well as decrease the aortic root growth And this strong, the
pharmacogenetic man of view, most often is effective for patients with apple insufficient notation not
the demeanor - this is the current finding of the functional Improvement. And that type of the mutation
mitosis direct us for see the predict the effect But unfortunately, Sex Therapy especially for the use of
Yeah, the earlier intervention is initiated the better the outcome. So let's achieve thing the Giving the
definitive diagnosis of Marfan syndrome is suggested to sort of patients can be earlier getting the
intervention.

The last. This is the pair of book of Mormon, it is as part of syndrome out like to talk about recipes. This
is our current research in the genetic groups that recipes is group of genetic disorders which is solved
from the germline mutation of identification in the grass and maybe capabilities. And in the example of
that. So, practice our Othello syndrome, modern Syndrome. Cardiovascular potential syndrome and
neurofibromatosis. So the PC server characteristics by distinct facial feature, a flamenco delays or
cognitive impairment and heart problems. So this is the involvement of genes in recipes. So here for the
arrest and mapk signaling, the location of the defective Gene can be various in here. For example, for
the Wrong. It can be caused by the mutation and various Source One of the most of the mutations are in
ptpn11 CBL raid 1 Etc. And by blocking the rust pathway will be beneficial for therapy. We can't
Authority. Get the cross if their upstream or Downstream to of the Rus mapk pathway. So, we can
expect the signaling canopy.

Result. Some drugs are now under development for an or in clinical trials, for example, the M EK
inhibitor, the tram a celebrity name. Then also the multiple kinase inhibitor density, need some other
drugs are currently under development. So, I also like to talk some about the NGS, our next Generation
sequencing, because with the advancements in the detection, for genomic variants. Now, we have the
Nexus, S sequencing which is the different between the NGS and Sanger sequencing is that the next-gen
sequencing Never. But analyze multiple multiple genes simultaneously and
So in here, we can have you can find variants in the multiple genes in one time. So, usually afford the
NGS base approach in cardiovascular, genetics will consist of three approach. The first is about the using
the targeted Gene panels. In you use a set of genes which is previously known as to have the correlation
or with the cause of the disease.

And then the exome sequencing were concerned, the series of clinical exome sequencing, which usually
consists of 5,000 to 7,000 clinically-relevant genes. So not only jeans with correlation with the
cardiovascular but also the other clinical phenotypes. And also we can do the whole exome sequencing
or it can Comfort all exams in our genome. We can also do whole genome sequencing if we can not
found any suspect that the variance in with the whole exome of or calculating panels, you can also do
the whole genome sequencing which we look at the whole genome to see the pathogenic variants. Fight
with the eggs on which can cause the difference in gene expression. For example, those variants in
promoter or in splice site. So understanding on the genetic basis on here, inherited cardiac condition is
needed to select the appropriate change to Green. But, Our effort, not only ended by finding the
variance but also we need to interpret the variants whether the variances photogenic on or likely
pathogenic the to be concluded as the cost of course, variance was our disease. So this is determining
the clinical importance of the variant that we found. It's a very, very generic likely pathogenic or rather
the bed but faryon is benign or likely benign or whether the variant has unspoken significant. So, for the
federal interpretation, we can use some Tools that are available online. For example, the clinvar
database, the genomic, religion database, where we can look for the frequency in population. Usually
those with likely pathogenic or pathogenic or very rare or ultra rare in the population. The course then is
2. And Everywhere You Go, various things, but of course, it might cause expensive and Everywhere You
Go, various things but this is the first area for clarification or we can go to the segregation and Rises the
more proof to get into the clinical description of it experience is very important. Sometimes that the
NGS that NGS.

That was the kiosk various so as I mentioned previously that not all you what was genetic, determination
that we do? We get the cost of divorce. Likely causative Gene, go for example, in the hypertrophic
cardiomyopathy only around 47 of until 72 percent across the fields and in some other part of my fatty
much lower Arc or us em. And we on only are we go. The get lost if we can get the genetic diagnosis for
getting disorders is sometimes 100%. So

Let me just say so good to summarize, what the British magazine workflow in genetic heart disease. So
when we see the patients, we have patients with certain genetic heart disease. We do the phenotyping
like collect the blood urine and brag or biopsy sample collections. The see the marker. Well, it That's
mine for the DNA for the variance. And yeah, we might do if you know typing just course is not only
clinical phenotype but also in deeper like we we look at the multi almost metabolomics, proteomics
transcriptomic holding genome And for more precise, you can also do the intro. This is modeling to see
whether this variant is really positive about the journey and then from that, we present a medicine
candidates. So from there, we can develop the novel therapies which is in here. We can test for these
people safety and efficacy.

Of the placement and then we can acquire the people strategy to the patients here in the right side of
the graph from the tip of the piping, we can get. This is marker information on this is marker. We might
find a novel biomarkers and from there, we can have accurately system going to be so. Let me go,
previous examples, are only a few part of fidelity suppression this in the IW L for precision medicine also
be in the form of other organisms for example using gene expression modulation using, for example, the
small inhibitory RNA synthetic micro RNA here Patient to In silencers. And we can also modify the genius
patient to using the molecule second. They can modify the transcription factors of the gene but also we
can affect the signal transduction using technical interruption modulators. We can also do the Jinn
anything for the disease which a single Gene.

10.22

Variants. And recently, the development of inter intra bodies, this is similar to antibodies. It is also in
development for the modalities operation addition. There are also the development of small molecules
which can also be the options. So in conclusion, the genetic component is the main feature in inherited
cardiovascular disease And direct the diagnosis and direct the clinical management. Although not every
testing will review the course on power from the diagnosis here. The tip prototyping is as much
important rest of the diagnosis and lead us to precess medicine and that Precision medicine in inherited
cardiovascular disease and be done to see step 4. To thank you for your attention and salam alaikum.

13.23

MP.

13.23

Oh, I said, Yeah, I have all the participation in the today, have a great day. And I have nice conference for
today, as the MC Dade about this afternoon decision, actually, we have three speakers. There is proper
any moderate map from his authority and props jealous of me for this afternoon decision as the And
then we have 45 minutes in each speakers and then we have 20 minutes for discussion but it s speaker.
Brookes uni is actually that we have questioned as a square in the last session. But actually proximities
cannot participate to eat during this guy sharing that all the participants in here, can type to the chat.
What kind of Do you want to access to proper facilities and then please type your email. So that's why.
After that proximity scan is energy per your request directly to your email but the fixation that property
has already joined

Association between periodontal disease, diabetes and cardiovascular That's probably me for today's
session, which like about the association between periodontal disease, diabetes, and cardiovascular
disease. And we can see in the screen that Prop Doctor anymore. Probably actually right now active as a
durability functional. That probably actually right now active as a professor and Department have open
your genetic Universe. It has a vlogger and then browse and you might know as the health department
of video dances baillio dense. Yeah, at longer your name. The city and properly have so many numerous
Publications and research grants and protect them. Yeah, we invited prepared me to speak properly
presentation. What do you find meaning this properly? It's time for years like that.

Association Thank you that benefit. Would you like I wrestled about association between better than
periodontal disease, theaters, and cardiovascular disease. I have to share 5050. Romantic right now. Do
not begin in Earnest. Thank you. Right.

In this year. And this is this day, I pretended up association association between periodontal disease,
diabetes, and cardiovascular disease. So right there it is very dental. Disease is representing a public
health problem effective about 22, Future of birth, or do the general exchange operation in cement,

But I don't eat, this is a chronic inflammatory diseases initiative by the presence of bacteria profile for
10.1.

The last several hours of evidence have supported the assistance of other Asian supermarket. Vegan,
paleo, don't leave this end system. A curved side.

Okay, elegy. Paraded with this is multifactorial the primary a theologian Factor. First immediate
inflammatory immune response and microbial truck and it's differentiable. And signs that says, if I sell
for a de-icer Lopez and genetic and And systemic disease. They met the progression of periodontal
disease. so intelligent it is inflammatory mechanism. of periodontal disease. So intelligent, it is
inflammatory mechanism. Dental work stimulates, local inflammatory. Its spell and lick its spell and
transliteration and amplification rocker million respondent plates to development of international and
research in progression of Predator that restriction and Bone resorption. So I so
We could be artist uses increase, periodontitis, and effects. The offer offer our hair and recent study,
suggesting that individual with periodontitis help increase risk of developing, diabetes, mellitus and
cardiovascular disease.

Yet this meditators and buried and it is also a two-way relationship excuses, on oral microbiota in a real
increase. The number, theorem that Terry get a purple polysaccharide are so increase in Munich
inflammatory reaction and in Press, This is a number. There are inflammatory, cytokine. So, increase,
press, skip insulin resistance, So, I Parade. But it really tastes increase race. THS to increase race race
such little plastic electricity bills. All right.

Periodontal disease and oral microbiome. Dispute is end of that. Increase risk Eco, a fifth disease risk
because it's right. In Balance, the 10th out, one disputes that is in RM, my you're procuring, third of four,
periodically things.

Right.

The epithelium on Prison top of it first. Hello Windham. Train of Hugh's. End of the field and xoto seen
into the bloodstream. The process leads the path area dissemination and systemic infection rate of
concept car.

Half-joking different information, release prostaglandin, eight months and increase bone resorption and
increase a chronic. Patate genetic dissemination and plus three months. It's a pair of stereo system and
Peripheral arterial disease. Right.

Let's just Dead good playing, but I don't like to this to address such threats including yet is the second
half you guys Square pieces. Very odd. Indeed. This increase 30 says, Press through LTI Pettis race. Right.

I have two to three times the race of effing ahead. Be a direct connection. Yes, right.
The mechanism is a direct and indirect. Direct Factory information to in detail. Indirect inflammatory
cytokine pursue Korea giddy in inflammatory. Need a 20 percent equity in the telephone going to test
for it.

Right. There are gender infection. Direct pathway that area a prop or indirect that way mahogany
Indepence release from that variable 41st. Japan is a toxin release from bacteria at grey cat detector at
the indomie septum connector. But that area introduction activity in a community system, because it so
Tito control inflammatory increase when the IMF Alpha plus start lending a to increase Ender Chest
stomach and increase and good passer. Responder say, reactive protein when increase in the liver so
increase sperm cells in endothelial, So, So, increase resik 0, 0 square assists. then intelligent 8, this
ended project the endothelial dysfunction. Yes endothelial dysfunction is independent. Vector of that,
you vascular? The pathologic process is usually caused by a direct use you availability in do it in smaller
Cossacks is a press of sign. In experiment marker in Britain because everybody had have constraints
there at use an electric correlate with the onset endothelial dysfunction. So

Application. Also. Attacks. Lung liquid ship. Boon to the surface of entertaining area. Sorry,

So another Andy of set that variable and addresses associated with the different carotid intima-media
thickness, and A substantial Improvement.

Vince. Amid. A diplomatic you study and it has suggested video to allow your potential first of throug
because antibody to and click active A after mistletoe commitments and putting on a ski lift release in
Orange for us for our pepper. It's true.

Antibodies at grains paid regardless significantly associated with good. It's a mixture.

And that's, I think a very identity token is also able to invade Daniel worse and cologne - Arturo sclerosis
but but it won't happen again and endotoxin then induce inflammatory response so I'll put my bed
inflammatory mediators are Post. Also potential for our walk up to, you quality system development, all
right?

For this reason, I fat dickhead policy should focus on Barry. O, don't need this and secure Fescue.
Learner this is a lab it this far through the Gimp and preventing and treating chronic infection. Let's in
combination with exercise, smoking control their identity when in the pension should be a fact and
release an integral part of add a program directed to Preston and more effectively manage. Yet mellitus
and cardiovascular disease. Select the implication of game dis, and family. Dakota after association
between periodontal and systematic pieces and the role of the LPS and family. Doctor is managing non-
communicable disease and promoting healthy lifestyle.

Then peace and family doctor. So collaborate in managing cardiovascular disease and diabetes mellitus.
And go ahead and check it out again. A a message a player he said come back I'm gonna tell them you
need Hello. On in Topeka, but yet in there but now get that you've asked me later. You see it again.
Thank you pick Anthony.