Cardiology Panels
Kristen K. Reynolds, PhD
VP Laboratory Operations
Copyright 2010 PGXL Laboratories, Louisville KY
All materials herein are the exclusive property of PGXL Laboratories
Panels*
Core:
Cardio Panel Add-Ons:
Thromobophilia:
CYP2D6
CYP2C9
CYP2C19
CYP3A4
CYP3A5
CYP1A2
VKORC1 (warfarin)
SLCO1B1 (statins)
FVL
FII
MTHFR
*All genes always orderable a la carte
Cardiology
Med List
CARDIOLOGY
Anti-Arrhythmics, Anti-Hypertensives
Amlodipine
Norvasc
Carvedilol
Coreg
Diltiazem
Cardizem
Felodipine
Plendil
Flecainide
Tambocor
Lercanidipine
Zanidip
Losartan
Cozaar
Metoprolol
Toprol-XL
Nifedipine
Adalat
Nisoldipine
Sular
Nitrendipine
Various brands
Propafenone
Rythmol
Propanolol
Inderal, various
Quinidine
Various brands
Timolol
Blocadren
Verapamil
Various brands
CYP3A4/CYP3A5
CYP2D6
CYP3A4/CYP3A5
CYP3A4/CYP3A5
CYP2D6
CYP3A4/CYP3A5
CYP2C9
CYP2D6
CYP3A4/CYP3A5
CYP3A4/CYP3A5
CYP3A4/CYP3A5
CYP2D6
CYP2D6
CYP3A4/CYP3A5
CYP2D6
CYP3A4/CYP3A5
Antithrombotics
Clopidogrel**
Rivaroxaban
Ticareglor
Warfarin
Plavix
Xarelto
Brilinta
Coumadin
CYP2C19
CYP3A4/CYP3A5
CYP3A4/CYP3A5
CYP2C9
Lipitor, Caduet
Lescol
Mevacor, Advicor
Compactin
Crestor
Zocor, Vytorin, Simcor
CYP3A4/CYP3A5
CYP2C9
CYP3A4/CYP3A5
CYP3A4/CYP3A5
CYP2C9
CYP3A4/CYP3A5
Statins
Atorvastatin
Fluvastatin
Lovastatin
Mevastatin
Rosuvastatin
Simvastatin
**indicates prodrug
CAD/Stents/TIA: Plavix (2C19)
Afib/Valve: Warfarin (2C9+VKORC1)
DVT/MI/Ischemic Stroke: thromobophilia risk (FVL, FII, MTHFR)
Hypertension/Arrhythmia:
Beta blockers, Ca Ch Blockers, ARBs (2D6, 2C9, 3A4/5)
Hyperlipidemia: Statins (CYP2C9, CYP3A4, CYP3A5, SLCO1B1)
Multi-drug use/ADR/Non-response:
2D6, 2C19, 2C9, VKORC1, 3A4, 3A5, 1A2, SLCO1B1
Genotype Frequency %
Gene
EM
IM
PM
UM
2D6
53
35
10
2
2C19
36
32
4
28
2C9
57
40
3
NA
3A4
87
12
1
NA
3A5
1
18
81
NA
The Problem
Reynolds et al. Pers Med 2007;4(1):11-31.
40% 2C9 deficient
>70% VKOR
sensitivity variant
Reynolds et al. Pers Med 2007;4(1):11-31.
n
i
r
a
.
0
2
.
4
1
.
8
W
0
0
1
.
2
0
0
.
6
0
0
.
0
0
a
3
-
r
f
Warfarin Genotyping
C
Y
P
2
C
9
C
Y
P
2
C
9
*
C
Y
P
2
C
9
*
S
CYP2C9 sets the rate,
affects time to SS
0
(accumulation and elimination)
0
3
6
9
1
21
T
51
i
82
m
0.8
(predicts warfarin sensitivity)
0.6
42
e
73
(
6.7 ± 3.3 mg
0.7
S-warfarin
VKORC1 sets the target
concentration
12
4.2 ± 2.2 mg
2.7 ± 1.2 mg
0.5
0.4
0.3
A/A
A/G
VKORC1
G/G
0
d
a
y
Warfarin Genotyping
Guides dose selection
–Estimates Maintenance Dose Requirement
Guides optimal INR interpretation
–Estimates Time to Reach Steady-State
CYP2C9 *2/*3
CYP2C9
Phenotype
Poor Metabolizer
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Decreased metabolic clearance expected.
Adjust Dosage
Adjustment
Phenytoin†
decrease 50%
Adjust based on multiple
factors
Warfarin†
VKORC1 GA
VKORC1
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Intermediate
Average VKORC1 enzyme expression and average warfarin dose requirement expected.
warfarin sensitivity
WARFARIN DOSE INFORMATION
Estimated time to steady-state: Delayed, 16-22 days
Estimated warfarin maintenance dose requirement: 3.9 mg/day‡ _
CYP2C9 Poor Metabolizer (PM): This patient’s genotype is consistent with significantly
reduced CYP2C9 enzymatic activity. Reduced CYP2C9 activity leads to lower dose
requirement (e.g., warfarin) due to decreased clearance, increased elimination half-life, and
increased time to reach steady-state blood concentrations.
VKORC1 Intermediate Warfarin Sensitivity: ‡The warfarin maintenance dose estimate was
derived using a published formula that accounts for age, gender, weight, and CYP2C9 and
VKORC1 genotypes. This estimate should be viewed as an example of how this information can
be taken into consideration by the physician as part of the overall patient management strategy.
CONFIDENTIAL COPYRIGHT PGXL LABORATORIES 2012
CYP2C9
Celecoxib
Celebrex
Ibuprofen
Advil, Motrin
Naproxen
Aleve
Glyburide
Diabeta
Glipizide
Glucotrol
Tolbutamide
Orinase
Glimepiride
Amaryl
Phenytoin
Dilantin
Fluvastatin
Lescol
Rosuvastatin
Crestor
Losartan
Cozaar
CONFIDENTIAL COPYRIGHT PGXL LABORATORIES 2012
Anti-platelet therapy
CYP2C19 - Plavix
Clopidogrel (Plavix) is a
PRODRUG
Active metabolite elicits
the desired antiplatelet
response
~ 30% of patients have
deficiency in CYP2C19
– Decreased amount of
active metabolite
– High on-treatment
platelet reactivity
Influence of CYP2C19 on Clopidogrel Response
Incidence of Adverse events in patients prescribed standard dosages of
Clopidogrel by CYP2C19 Phenotype.
PHENOTYPE
Stent Thrombosis
EM
CV death, MI,
Ischemic Stroke
8%
(BASELINE)
8.9%
1.4%
IM
10%
2.4%
PM
12.7%
5.7%
Mega et.al., JAMA. 2010;304(16);1821-1830.
0.9%
Gene-Dose dependency of therapeutic platelet inhibition
Mega et al. JAMA 2011;23/30; 306(20)
Cost-effectiveness
• Cost model based on event occurrence in TRITON-TIMI 38
Treatment
CV Events
Bleed Events
ICER
Genotype guided
813
340
Clopidogrel
1210
380
$ 6,790
$2.9M
Prasugrel
990
500
$ 11,710
$3.9M
• Genotype-guided therapy selection may be more cost effective and lead to
fewer adverse outcomes
Reese, E.S. et. al., Pharmacotherapy 2012;32(4):323–332
2C19
CYP2C19 *2/*2
CYP2C19
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Poor Metabolizer Avoid
Clopidogrel**
Alternative Consideration
Adjust Dosage Adjustment
Prasugrel
Imipramine†
Sertraline†
decrease 30%
decrease 50%
**Lack of efficacy due to failure to produce active metabolite; †Increased risk of adverse events due to
diminished drug clearance.
CYP2C19 Poor Metabolizer (PM): This patient’s genotype is consistent with significantly
reduced CYP2C19 enzymatic activity. PMs are at increased risk of drug-induced side effects
due to diminished drug elimination of active drugs. Patients with no CYP2C19 function (PMs)
taking clopidogrel lack adequate antiplatelet response and remain at risk for cardiovascular
events, including thrombosis, myocardial infarction, stroke, and death.
CONFIDENTIAL COPYRIGHT PGXL LABORATORIES 2012
2C19 all
RESULTS
Gene
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Phenotype
Avoid
Alternative Consideration
Adjust Dosage
Adjustment
†
Caution, consider 30%
Caution, consider 50%
†
30%
50%
! CYP2C19
*1/*2
Intermediate
Metabolizer
Clopidogrel*
Prasugrel
Imipramine
†
Sertraline
X CYP2C19
*2/*2
Poor
Metabolizer
Clopidogrel*
Prasugrel
Imipramine
†
Sertraline
X CYP2C19
*17/*17
Ultra-Rapid
Metabolizer
Increased metabolic clearance expected. Possible
increased risk of bleeding events with clopidogrel.
 CYP2C19
*1/*1
Extensive
Metabolizer
Normal metabolic clearance expected.
up to 150%
Citalopram
†
up to 150%
Escitalopram
†
100-200%
Omeprazole
†
50-100%
Esomeprazole
†
200%
Lansoprazole
†
400%
Pantoprazole
Common CYP2C19 medications next page
! CYP2C19
*2/*17
Or *3/*17
Intermediate
∫
Metabolizer
Decreased metabolic clearance expected based on
presence of the inactive allele.
Imipramine
†
Sertraline
†
†
Caution, consider 30%
Caution, consider 50%
CYP2C19
Clopidogrel
Citalopram
Escitalopram
Imipramine
Sertraline
Diazepam
Omeprazole
Esomeprazole
Pantoprazole
Rabeprazole
Lansoprazole
Nelfinavir
Plavix
Celexa
Lexapro, various
Tofranil
Zoloft
Valium
Prilosec
Nexium
Protonix
Aciphex
Prevacid
Viracept
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Statin Therapy
Statin therapy reduces risk of CV events
Statin therapy can lead to muscle weakness
– Myalgia
– Myopathy
– Rhabdomyolysis
Genotyping can guide statin choice and dose
CYP3A4 and 3A5
Together metabolize 50% of all medications
80% redundancy of function
Genetic variants in each
– decrease enzyme function (clearance)
– Increased risk of dose-dependent adverse events
CYP3A4/5
master
drug list
CYP3A4/CYP3A5 Substrates
PSYCHIATRY
Benzodiazepines
Alprazolam
Xanax
Midazolam
Versed
Triazolam
Halcion
Antipsychotics
Quetiapine
Seroquel
Ziprasidone
Geodon
Buspirone
Buspar
Lurasidone
Latuda
Carbamazepine
Various brands
Antidepressants
Desvenlafaxine
Pristiq
Vilazodone
Viibryd
Trazadone
Desyrel
Nefazadone
Serzone
Reboxetine
Edronax
Nortriptyline
Pamelor, Aventyl
CARDIOLOGY
Quinidine
Ticareglor
Rivaroxaban
Statins
Atorvastatin
Lovastatin
Mevastatin
Simvastatin
Ca Channel Blockers
Amlodipine
Diltiazem
Felodipine
Lercanidipine
Nifedipine
Nisoldipine
Nitrendipine
Verapamil
Various brands
Brilinta
Xarelto
Lipitor, Caduet
Mevacor, Advicor
Compactin
Zocor, Vytorin, Simcor
Norvasc
Cardizem
Plendil
Zanidip
Adalat
Sular
Various brands
Various brands
OTHER
Antimicrobials/antivirals
Clarithromycin
Erythromycin
Telithromycin
Indinavir
Nelfinavir
Ritonavir
Saquinavir
Biaxin
E-Mycin
Ketek
Crixivan
Viracept
Norvir
Fortovase
Steroids
Estradiol
Hydrocortisone
Progesterone
Testosterone
Various brands
Various brands
Various brands
Various brands
Chemotherapeutics
Vincristine
Docetaxel
Oncovin
Taxotere
Pain Management
Cyclobenzaprine
Fentanyl
Alfentanil
Flexaril
Actiq, Duragesic
Alfenta
Immunosuppressants
Cyclosporine
Tacrolimus
Gengraf
Prograf
CYP3A4/5 significant variants
CYP3A4*22
– Decreased dose requirements for tacrolimus,
cyclosporin, simvastatin, atorvastatin, lovastatin,
midazolam
– 4-8% frequency
CYP3A5*3
– Decreased dose requirements vincristine, tacrolimus,
cyclosporin
– 90% freq Cauc, 50% AA, 60% Asians
3A4 Interpretation
CYP3A4
Phenotype
Extensive
Metabolizer
CYP3A4
Phenotype
Partially
Decreased
Metabolizer
CYP3A4
Phenotype
Decreased
Metabolizer
CYP3A4
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Normal metabolic clearance expected. Common CYP3A4 medications below.
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Decreased metabolic clearance expected with increased risk of dose-dependent side
effects. Common CYP3A4 medications below.
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Decreased metabolic clearance expected with increased risk of dose-dependent side
effects. Common CYP3A4 medications below.
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Adjust Dosage
*22
Decreased metabolic clearance expected Simvastatin
Decreased with increased risk of dose-dependent side
Atorvastatin
Metabolizer effects.
Lovastatin
Tacrolimus
Adjustment
max 10-20 mg, or consider
alternative statin if also
SLCO1B1 *5/*5 genotype
max 10-20 mg
max 10-20 mg
decrease by up to 40%
3A5 Interpretation
CYP3A5
Phenotype
Extensive
Metabolizer
CYP3A5
Phenotype
Partially
Decreased
Metabolizer
CYP3A5
Phenotype
Decreased
Metabolizer
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Genotype consistent with the highest baseline enzymatic activity for CYP3A5. Patients with
this genotype represent only 1% of the population. Maintenance dosages for most
CYP3A5 drugs may be at the higher end of the typical dose range. Common CYP3A5
medications below.
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Genotype consistent with intermediate CYP3A5 enzymatic activity and represents
approximately 20% of the population. For PDMs, maintenance dosages for most CYP3A5
drugs are lower than extensive metabolizers and are higher than decreased metabolizers.
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Genotype consistent with reduced CYP3A5 enzymatic activity and represents the majority
(60-80%) of the population. For DMs, maintenance dosages for most CYP3A drugs are
lower than extensive metabolizers. Common CYP3A5 medications below.
SLC01B1
OATP1B1
~35% of population are carriers of the SLC01B1*5 allele
– Myalgia/muscle cramps
Myopathy on 40mg/day:
– SLCO1B1 *1/*5, OR = 2.6
– SLCO1B1 *5/*5, OR = 5.2
Most frequently associated with simvastatin > atorvastatin >
pravastatin
Vanderbilt
Algorithm
Wilke et al. Clin Pharmaco Ther 2012;92(1).
Statin Combo Interpretation
CYP3A4
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Adjust Dosage
*22 Decreased Decreased metabolic clearance expected with
Metabolizer increased risk of dose-dependent side effects.
SLCO1B1
Phenotype
Simvastatin
Atorvastatin
Lovastatin
Tacrolimus
Adjustment
max 10-20 mg, or consider
alternative statin if also SLCO1B1
*5/*5 genotype
max 10-20 mg
max 10-20 mg
decrease by up to 40%
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Avoid
>5 Fold
Increased
Simvastatin
Myopathy Risk
Alternative Consideration
pravastatin, lovastatin,
fluvastatin, rosuvastatin,
mevastatin
Adjust Dosage
Adjustment
Atorvastatin
max 10-20 mg
Anti-arrhythmics
and
Anti-hypertensives
3A4: Ca++ Channel Blockers
Amlodipine
Diltiazem
Felodipine
Lercanidipine
Nifedipine
Nisoldipine
Nitrendipine
Verapamil
CYP3A4
Phenotype
Extensive
Metabolizer
CYP3A4
Phenotype
Partially
Decreased
Metabolizer
CYP3A4
Phenotype
Decreased
Metabolizer
Norvasc
Cardizem
Plendil
Zanidip
Adalat
Sular
Various brands
Various brands
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Normal metabolic clearance expected. Common CYP3A4 medications below.
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Decreased metabolic clearance expected with increased risk of dose-dependent side
effects. Common CYP3A4 medications below.
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Decreased metabolic clearance expected with increased risk of dose-dependent side
effects. Common CYP3A4 medications below.
CYP2D6
CYP2D6 *4/*4
CYP2D6
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Poor Metabolizer
Avoid
Codeine**
Hydrocodone**
Oxycodone**
Tramadol**
Tamoxifen**
Amitriptyline †
Venlafaxine †
Risperidone †
Alternative Consideration
Adjust Dosage
Adjustment
Morphine, non-opioid
Hydromorphone, non-opioid
Oxymorphone, non-opioid
Consider active drug, non-opioid
Anastrozole, exemestane, letrozole
Citalopram, sertraline
Citalopram, sertraline
Quetiapine, olanzapine, clozapine
Aripiprazole †
10 mg/day maximum
decrease 50%
decrease 60%
decrease 50%
decrease 50%
decrease 70%
decrease 60%
decrease 70%
decrease 75%, or
atenolol, bisoprolol,
carvedilol
decrease 50%, or
flupenthixol, quetiapine,
olanzapine, clozapine
Clomipramine †
Doxepin †
Flecainide †
Haloperidol †
Imipramine†
Nortriptyline †
Propafenone †
Metoprolol †
Zuclopenthixol †
**Lack of efficacy due to failure to produce active metabolite; †Increased risk of adverse events due to
diminished drug clearance.
CONFIDENTIAL COPYRIGHT PGXL LABORATORIES 2012
RESULTS
Gene
X CYP2D6
*4/*4
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Phenotype
Poor
Metabolizer
Avoid
Codeine*
Hydrocodone*
Oxycodone*
Tramadol*
Normal metabolic clearance expected.
Adjustment
10 mg/day maximum
50%
60%
50%
50%
70%
60%
70%
75%, or atenolol, bisoprolol,
carvedilol
†
Zuclopenthixol
50%, or flupenthixol,
quetiapine, olanzapine,
clozapine
Common CYP2D6 medications next page
Oxycodone*
Hydrocodone*
†
Propafenone
Oxymorphone, non-opioid
Hydromorphone, non-opioid
Sotalol, disopyramide,
quinidine, amiodarone
Quetiapine, olanzapine,
clozapine
Citalopram, sertraline
Codeine*
Tramadol*
Tamoxifen*
Morphine, non-opioid
Hydromorphone, non-opioid
Oxymorphone, non-opioid
Citalopram, sertraline
Citalopram, sertraline
Citalopram, sertraline
Methylphenidate
Quetiapine, olanzapine,
clozapine
Flupenthixol, quetiapine,
olanzapine, clozapine
Sotalol, disopyramide,
quinidine, amiodarone
Tramadol*
†
Imipramine
†
Nortriptyline
†
Venlafaxine
Tamoxifen*
Amitriptyline
†
Venlafaxine
†
Risperidone
 CYP2D6
*1/*1
! CYP2D6
*1/*4
Extensive
Metabolizer
Intermediate
Metabolizer
Risperidone
†
†
†
Velafaxine
X CYP2D6
*1/*1xN
Ultra-Rapid
Metabolizer
Codeine*
Hydrocodone*
Oxycodone*
†
Amitriptyline
†
Clomipramine
†
Paroxetine
†
Atomoxetine
†
Risperidone
Zuclopenthixol
Propafenone
†
†
Alternative Consideration
Morphine, non-opioid
Hydromorphone, non-opioid
Oxymorphone, non-opioid
Consider active drug, nonopioid
Anastrozole, exemestane,
letrozole
Citalopram, sertraline
Citalopram, sertraline
Quetiapine, olanzapine,
clozapine
Adjust Dosage
†
Aripiprazole
†
Clomipramine
†
Doxepin
†
Flecainide
†
Haloperidol
†
Imipramine
†
Nortriptyline
†
Propafenone
†
Metoprolol
†
Amitriptyline
†
Imipramine
†
Nortriptyline
†
Zuclopenthixol
†
Doxepin
†
Flecainide
†
Metoprolol
Haloperidol
†
†
Doxepin
†
Metoprolol
15-60 mg/hr
titrate to pain relief
Avoid CYP2D6 inhibitors, e.g.
paroxetine, or consider
aromatase inhibitor in postmenopausal women
25%
30%
40%
25%
20%
25%
50%, or atenolol, bisoprolol,
carvedilol
30%
70%
60%
150%, or citalopram,
sertraline
based on plasma
measurement, or pimozide,
flupenthixol, fluphenazine,
quetiapine, olanzapine,
clozapine
100%
up to 250%, or atenolol,
bisoprolol, carvedilol
CYP2D6
Pain Management
Codeine**
Oxycodone**
Hydrocodone**
Tramadol**
Various brands
Oxycontin, various
Various brands
Ultram, various
Cardiology
Carvedilol
Metoprolol
Propanolol
Timolol
Propafenone
Flecainide
Coreg
Toprol-XL
Inderal, various
Blocadren
Rythmol
Tambocor
Other
Loratadine
Donepezil
Dextromethorphan
Tamoxifen**
Claritin
Aricept
Various brands
Various brands
Psychiatry
Antidepressants
Fluoxetine
Fluvoxamine
Paroxetine
Venlafaxine
Duloxetine
Maprotiline
Mirtazapine
Amitriptyline
Clomipramine
Desipramine
Doxepin
Imipramine
Nortriptyline
Trimipramine
Prozac
Luvox
Paxil
Effexor
Cymbalta
Ludiomil
Remeron
Various brands
Ananfranil
Norpramin
Sinequan
Tofranil
Pamelor,
Aventyl
Surmontil
CONFIDENTIAL COPYRIGHT PGXL LABORATORIES 2012
Antipsychotics
Haloperidol
Risperidone
Aripiprazole
Zuclopenthixol
Perphenazine
Thioridazine
Iloperidine
Chlorpromazine
Atomoxetine
Amphetamine
Haldol
Risperidol
Abilify
Various brands
Trilafon
Mellaril
Fanapt
Thorazine
Strattera
Adderall
Thrombophilia
panel
Thrombophilia Panel
• Factor V Leiden
• Factor II (prothrombin)
• MTHFR
X Factor V
Leiden
AA
>9 fold
Increased
Thrombosis
Risk
Female, Positive family history of thrombotic events:
avoid estrogen-containing oral contraceptives and
consider alternative contraceptive (e.g., IUD or
progestin-only contraceptive).
! Factor II
GA
2-3 fold Increased Thrombosis Risk
X MTHFR
677 TT
1298 AA
Increased
Risk
Negative family history of thrombotic events:
avoid additional risk factors (e.g., obesity,
smoking).
Increased risk of hyperhomocysteinemia, coronary artery disease, and thrombosis when folate deficiency is
present. Consider folate supplementation.
Factor V Leiden High Thrombosis Risk: This genotype result revealed that the patient is homozygous for (has two copies
of) the Factor V Leiden (1691 G>A) variant, which has been associated with an increased risk of thromboembolic events.
This variant is found in approximately 4% of individuals in the U.S. Presence of the Factor V Leiden variant increases the
risk of venous thromboembolism (VTE) by 3-8 fold in heterozygous carriers and >9 fold in homozygous carriers.
Factor II Moderate Thrombosis Risk: This genotype result revealed that the patient is heterozygous for (has one copy of) the
Factor II (Prothrombin) 20210 G>A variant, which has been associated with an increased risk of thromboembolic events. This
variant is found in approximately 2% of individuals in the U.S. Presence of the Factor II 20210G>A variant increases the risk of
venous thromboembolism (VTE) by 2-3 fold in heterozygous carriers and >3 fold in homozygous carriers.
MTHFR Increased Risk: Presence of the 677 C>T polymorphism of MTHFR leads to decreased MTHFR enzymatic activity and
elevated homocysteine. This patient’s genotype is consistent with an increased risk of hyperhomocysteinemia, atherosclerotic
heart disease, myocardial infarction, cerebrovascular disease, and venous thrombosis. Additionally, associations between the
677 C>T polymorphism and increased risk for methotrexate toxicity, increased 5-fluorouracil chemosensitivity, and increased
risk of fetal neural tube defects in pregnant women have also been reported in states of folate deficiency.
Thank You!
kreynolds@pgxlab.com