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Genomics for Patient CareSharon Hausman-Cohen, MD, AAFP, ABIHM
Board Certified in Family Medicine and Integrative Medicine
Speaker Disclosure
Dr. Hausman-Cohen has disclosed that she is an employee of In-Depth DNA.
Learning Objectives
By the end of this activity, the participant should be better able to:
1. Discuss the difference between genetic diseases and Genomic SNPS and how SNPS can help guide medical care.
2. Utilize cardiac related genomics to determine what interventions might best benefit patients.
3. Discuss the etiology of macular degeneration by looking at its genomics and how this can guide supplements.
4. Be comfortable with some of the ethical, emotional and legal issues regarding the field of genomics.
Genetics: Study of Genes and Their Inheritance
Genetic diseases can be due to: Duplications of chromosomes (Trisomy 21) Nucleotide repeats of pieces of chromosomes (Huntington’s = CAG
repeat of 36-100 times vs normal 10-35 times) Deletions (Turner’s syndrome is partial or missing X chromosome) Single nucleotide genomic variants (over 30 of the 60 forms of Tay-
Sachs)
GENOMICS
Genomics: Characterization and quantification of genes, which direct the production of proteins with the assistance of enzymes and messenger molecules.
Genomic variants in DNA can create protein or enzyme product that is less efficient or non-functional.
Examples:○ Catecholamine transferase (COMT) – Val/Met alleles decreases
break down of cortisol and dopamine activity by 4-5 fold.○ Glycoprotein 6 (GP6) – CC alleles decrease platelet activation by
56%.
TranscriptionDNA TranslationRNA Protein
Central Dogma of Genomics
DNA creates RNA, which creates proteins Small DNA changes (SNPs) can have
profound effects on protein production and function
Single nucletide polymorphisms (SNPs)
Nomenclature Refresher: DNA & Chromosomes
Chromosomes are found in the nucleus of each cell.
Chromosomes are made of o DNA, a double-stranded helix composed
of sugar, phosphate, and nitrogenous base.
o Base pairs are formed by the following nitrogenous bases Arginine(A)-Thymine(T) and Cytosine(C)-Guanine(G).
Human genome is comprised of approx. 3 billion base pairs
Genes are portions of DNA molecules that serves as the basic unit of heredity.
Nomaclature Refresher: Alleles
An allele is one of two or more versions of a gene that is expressed. An individual inherits two alleles for each gene, and thus can be
homozygous for that allele or heterozygous. The major allele is the more prevalent allele; the minor allele is less
prevalent. Not all minor variants are “risk mutations.” Some may convey benefit.
The Difference Between the Major and Minor Allele is Generally Due to a SNP
Single nucleotide polymorphism (SNP) is a change in one nucleotide within a stretch of DNAo Can have no significant health effecto Can have a significant metabolic/health effect if: Variant occurs in a region that changes gene transcription Variant alters protein structure
o Occurs about once in every 300 base pairso Occurs between or within genes
How are SNPs and Genes Named?
Reference SNP ID numbers (“rs” ID) are assigned to groups of SNPs that map to specific locations.
Gene names often relate to the function of the gene.
Examples:
VDR: Vitamin D receptor
COMT: Catecholamine transferase
NOS: Nitric oxide synthase
MTHFR: Methytetrahydrofolate Reductase
SNPs & Pathology
In some cases, SNPs have significant implicationso F5 (Factor V), HFE C282Y (hemochromatosis)
Most health risks (cardiac, macular degeneration, melanoma) are polygenic (along with epigenetics from lifestyle and environment)
Example: One copy of F5 factor 5 Leiden is actionable
• Understanding the genomics of health risk provides targets for intervention
• DVT prophylaxis
○ Enoxaparin for international flights
○ Compressing stockings
○ Aggressive surgical prophylaxis
○ If combined with other SNPs, can have additive risk
Approach to Utilizing Genetic Information in Family Medicine = Personalized Medicine
1. Identify SNPs associated with a particular health risk.
2. Utilize the odds ratio for health risk based on patient genetic profile in guiding medical decision making.
3. Customize interventions based on their genomics, research, and discuss with patient.
Case Study 1: Cardiovascular Disease
Cardiovascular Disease: Genetics Overview
• Risk for CVD may be increased due to SNPs associated with:○ Increased in arterial stiffness○ Increased Lp(a) ○ Increased cholesterol particle size and
number ○ Decreased HDL levels○ Vascular inflammation and oxidative
stress • SNPs that decrease platelet aggregation
may be cardioprotective
Personalized Medicine:A Case Study
• Family hx: • Father: Heart disease at age 67• Paternal uncle and paternal
grandmother: Heart disease in their 50s.
• Mother: Alzheimer’s• Currently on rosuvastatin 20mg and
enalapril 10mg• LDL 126, glucose 115, hs-crp 1.4• Hates doctors, LOVES to exercise• Willing to add “1 or 2 things” to decrease
risk.
MARK: 66 year old busy business executive with hypertension, high cholesterol, and gout.
RiskSNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs13… CDKN2A/2B (ANRIL/9p21)
C CC 2 1.2 CG1.5 CC
Increases arterial stiffness;1.7x increase risk of sudden cardiac death in men
rs10… CDKN2A/2B (ANRIL/9p21)
G GG 2 1.5 GA2.0 GG
Cyclin dependent kinase inhibitor; Odds ratio of1.8 for sudden cardiac death in men
rs10… LPA G AA 0 1.7 AG2.57 GG
Increases Lp(a), Inhibits TPa.
Any combination of 2 or more variants = 2.57 –4.87 OR.
rs37… LPA C TT 0 1.9 CT2.6 CC Carriers benefited from aspirin with 56% reduction
in cardiac events.
rs70… IL33 T TT 2 1.39 In promotor of IL33, part of IL1 family.
IL33 IL1RL Additive OR
TT GG 4.98
TT GA 2.39
rs11… IL1RL G AG 1 1.40 TC GG 2.4
TC GA 1.92
IL1 receptor ligand. Involved in vascular inflammation.
Benefit SNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs70… CETP A AG 1 0.71 AG0.55 AA
Lower CETP activity correlated high HDL
Addressing Cholesterol and Cardiac Stiffness
• Lab/Genomics Findings○ CDKN2A/2B (ANRIL gene)
• Interventions based on CDKN2A/2B○ ACE inhibitor
○ Curcumin
○ Vitamin K2
ACE Inhibitors Good Choice with CDKN2A/2B:ACE Inhibitors Reduce Arterial Stiffness
• ACE Inhibitors: o Reduced pulse wave velocity (p<0.00001)o Significantly reduced Augmentation Index (AIx) (p=0.0006)o 7 trials: Significantly reduced AIx compared to beta blockers (p= 0.002)o 10 ACE Inhibitors significantly improved brachial FMD, (p=0.002)o 11 trials: Treatment with ACE Inhibitors had a significant effect on
brachial FMD compared to other antihypertensive drugs (p=0.009)
Yousef Shahin MD
* https://ww
w.researchgate.net/publication/257581144
Curcumin and Arterial Compliance
Curcumin along with aerobic exercise training
has been shown to decrease arterial
compliance in as little as 8 weeks.
“Effects of curcumin intake and aerobic exercise training on arterial compliance in postmenopausal women”, Artery Research 7 (2013), February 2013
Vitamin K2: Health & Compliance of Aorta Post Mortum Correlates to Vit K2 levels http://w
ww
.drpasswater.com
/nutrition_library/Schurgers.htm
lRelationship Between Vit K2 levels and atherosclerosis from Netherland’sStudy: (Dr. Schurgers)
2004 Rotterdam Heart Study:
• Tracked 4,800 participants for 10 years.• Participants who ingested the largest quantity of vitamin K2
in their diet experienced 57% reduction in death from heart disease than people who ingested the least. R
eferences: J Nutr;2004 N
ov: 134(11)3100-5.
Dietary Intake of Vitamin K2 Inversely Associated with Mortality Risk: PREDIMED
Juanola-Falgarona et al. J Nutr 2014
Prospective cohort• N = 7216 (CVD risk)• Age: 55-80 year old• Q1 = 171 g/d• Q5 = 626 g/d
CardiovascularHR: 0.63
All-CauseHR: 0.64
CancerHR: 0.54
KING Trial (Vitamin K2 in Renal Graft)
• Renal transplant recipients (N = 60)
• 8 weeks of menaquinone7 (vitamin K2) supplementation (360 μg QD)
• Arterial stiffness was measured using carotid femoral pulse wave velocity (cfPWV).
• Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks
• Vitamin K Increased phosphorylated matrixGla protein.
Mansour AG et al. Vitamin K2 supplementation and arterial stiffness among renal transplant recipients – a single-arm, single-center clinical trial. J Am Soc Hypertens. 2017 Jul 13. Pii: S1933-1711(17)30255-3.
Addressing Inflammation: IL33/ IL1RL1(ST2)
• Curcumin – active ingredient ethyl acetate
• Scavenges free radicals
• Reduces LDL oxidation
• Anti-inflammatory effects
• Anti-thrombotic
J Food Sci Technol. 2014 Dec;51(12):3910‐7. doi: 10.1007/s13197‐013‐0953‐7. Epub 2013 Feb 15.Int J Cardiol. 2009 Apr 3;133(2):145‐51. doi: 10.1016/j.ijcard.2009.01.073. Epub 2009 Feb 23
▣ Only child
▣ Family history essentially unknown from cardiac standpoint due to mother dying 55 from lung cancer and father died 70s from unknown infection
○ Currently on Nature throid, L-methylfolate, iodine, and Vitamin D and K
Personalized Medicine:A Case Study
Molly: 70 year old Artist. Macular Degeneration, hypothyroidism, MTHFR mutation, and hyperlipidemia.
RiskSNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs13… CDKN2A/2B (ANRIL/9p21)
C CG 1 1.2 CG1.5 CC
Increases arterial stiffness;1.7x increase risk of sudden cardiac death in men
rs10… CDKN2A/2B (ANRIL/9p21)
G AG 1 1.5 GA2.0 GG
Cyclin dependent kinase inhibitor; Odds ratio of1.8 for sudden cardiac death in men
rs10… LPA G AG 1 1.7 AG2.57 GG
Increases Lp(a), Inhibits TPa.
Any combination of 2 or more variants = 2.57 –4.87 OR.
rs37… LPA C TT 0 1.9 CT2.6 CC Carriers benefited from aspirin with 56% reduction
in cardiac events.
rs70… IL33 T TT 2 1.39 In promotor of IL33, part of IL1 family.
IL33 IL1RL Additive OR
TT GG 4.98
TT GA 2.39
rs11… IL1RL G AG 1 1.40 TC GG 2.4
TC GA 1.92
IL1 receptor ligand. Involved in vascular inflammation.
Benefit SNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs70… CETP A AA 2 0.71 AG0.55 AA
Lower CETP activity correlated high HDL
CVD: LPA Based Intervention is Aspirin
• LPA variants correlate with lower tissue plasminogen activator levels and higher Lp(a). Competitively inhibits tPA and increases thrombosis risk related to arterial damage
• 90% of elevated Lp(a) may be due to genetic variation.
• Aspirin has been shown to decrease risk of cardiac events in women with high Lp(a) by 56%.
• Carriers of LPA snps (elevated Lp(a)) had 56% reduction (p=.0001) in Cardiac Events with aspirin and non carriers had only 9% reduction (ns).
http://www.lipoproteinafoundation.org/?page=AspirinandLpa
CVD: Don’t Forget Alleles Can Be
Beneficial
• Benefit allele GP6 (glycoprotein 6): 2 copies○ Decreases recurrent cardiac events by 19%○ Associated with a 27% decrease in all cause mortality○ Decreases platelet aggregation
• For patients with two copies of GP6 (GG):○ Post-MI use of aspirin may have limited benefit
• In all other cases (GC and CC genotypes), aspirin use is recommended following MI
Case Study 2: Melanoma
Melanoma: Genetics Overview
Develops from a dysregulation of melanocyte proliferation that makes melanocytes unresponsive to regulatory signaling pathways
One major trigger is UV-induced DNA damage Compared to other skin cancers, melanoma has much higher rates of metastasis
and mortality New biological regimens can be life saving Anyone diagnosed with melanoma should consult with an oncologist familiar with
these treatments
Personalized Medicine:Case Study: Renee
Renee: 48 year old RN. Came in for preventive concerns.
Family History
• Father had 3 melanomas, heart disease, and arthritis.
Medications: Curcumin, potassium, and vitamin D
RiskSNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs18… MC1R T CC 0 4.38 “Red hair” variant, associated with freckles and sun sensitivity
rs25… CDK10 G GG 2 2.26 Pigment association gene.
rs18… MYH7B G GG 2 2.22 Pigment association gene.
rs49… ASIP G AA 0 1.79 Pigment association gene.
rs40… CLPTM1L T CT 1 1.60 Important in apoptosis signaling.
rs10… MC1R T GG 0 1.59 “Red hair” and pigment associated gene.
Benefit SNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs70… SLC45A2 G GG 2 0.51 Influential on skin pigmentation. Regarded as an informative marker for ancestry. Associated with
dark skin, eye, and hair color in Caucasians.
rs22… MTAP T CC 0 0.74 This gene is often co-deleted with a tumorsuppressor gene (p16), deficiencies areassociated with many types of cancer.
Melanoma: Renee
Melanoma: Genetics-Based Interventions
Curcumin (300-1000 mg BID)o Derived from tumerico Anti-inflammatory and antioxidant effectso Reduces risk of neogenesis via inhibition of angiogenesis, induction of
apoptosis (targets p53), and induction of cell adhesion Genistein (28 mg BID with food)
Isolated from soybeans Can inhibit cell cycle progression & promote apoptosis in melanoma cells
(targets p53 and p21) Inhibits AKT & MAPK (proteins involved in signaling pathways)
*research and interventions courtesy of Dr. William LaValley
Melanoma: Genetics-Based Interventions,
Continued
Epigallocatechin Gallate (EGCG) (750 mg 1-2x/day)○ Isolated from green tea○ Reduces growth○ Inhibits migration of melanoma cells (inhibits Nf-
kappaB, COX-2, and PGE2)○ Modulates cyclin dependent kinase and Bcl-2 family
proteins○ Does not exert an effect on the growth of normal
melanocytes, & may decrease tumor angiogenesis
Melanoma: Genetics-Based Interventions,
Continued
Quercetin○ Found in a variety of fresh fruits and vegetables.○ Variety of antiproliferative effects, including
promotion of apoptosis in cancerous cells○ Metabolized into compound that promotes the
inhibition of tyrosinase (pigmentation pathway enzyme linked to tumor formation)
○ Reduction of MMP-9 expression (degrades extracellular matrix), and pro-oxidant effects
Melanoma: Genetics-Based Interventions, Continued
Sulforaphane○ Isolated from broccoli sprouts○ Contains antioxidant properties (via the glutathione pathway)○ Anti-inflammatory properties (via inflammasome modification) ○ Anti-cancer properties, including proapoptotic activities○ Inhibition of cell growth
Vitamin D (10,000 IU/day or 50,000 IU/week)○ Low serum levels of vitamin D are associated with an increased risk of melanoma
progression○ Maintaining a vitamin D level ≥40 ng/ml has been associated with 67% less overall
risk of cancers compared with a level of ≤20 ng/ml
Case Study 3: Macular Degeneration
Macular Degeneration: Genetics Overview
• Age-related macular degeneration (AMD) is a result of overactivation of complement system (group of proteins that play key role in immune response), which causes formation of drusen in eyes
• Many SNPs that increase risk for AMD cause overactivation of complement system.
• Protective SNPs, meanwhile, frequently suppress the complement system.
Oxidative Stress is Another Factor in Macular Degeneration
Oxidative stress contributes to Macular Degeneration
Personalized Medicine:Case Study
Susan: 48 year old Researcher. Went in for a annual physical and amsler grid was slightly wavy.
• Amsler grid screening showed mild fading and bending of lines.
• No family history of macular degeneration.• Mother with familial drusen and cataracts. • Sister with retinal detachments
RiskSNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs10… ARMS2-HTRA1
T GT 1 3.19 Retinal pigment levels decreased (lower levels are more at risk for AMD). Geographic atrophy.
Choroidal neovascularization. If patient is a smoker, OR increase up to 15.7.
rs11… HTRA1 A N/A N/A 3.97
rs10… CFH G AG 1 2.43 Complement factor H. Multiple variant SNPs can have additive risk or more significant risk if no
benefit alleles in CFH pathway.
rs49… CFH (Y402H) C N/A N/A 2.0-11.0 Complement factor H. Vitamin A can INCREASE drusen risk up to 3.27 with variants.
rs22… C3 C CG 1 1.42 Complement component 3.
Benefit SNP
Gene Benefit Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs93… C2 C GG 0 0.46
Complement pathway. Associated with less aggressive complement activation.
rs80… CFH A TT 0 AG 0.65AA 0.41
rs14 CFH G AG 1 0.70 AG0.40 GG
rs42 CT-CFB (SKIV2L)
A AG 1 0.24-0.49
Protective against neovascular (wet AMD)
AMD: Susan
• Worries about her eyes more than anything as an artist
• Wonders if she really can take the aspirin for her heart as she does not want to progress to wet AMD
• Would like to know if there is anything else she can do for her eyes
• On AREDS2 supplement
Personalized Medicine:Back to Molly
Molly: 70 year old Artist. Macular Degeneration, hypothyroidism, MTHFR mutation, and hyperlipidemia.
RiskSNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs10… ARMS2-HTRA1
T GT 1 3.19 Retinal pigment levels decreased (lower levels are more at risk for AMD). Geographic atrophy.
Choroidal neovascularization. If patient is a smoker, OR increase up to 15.7.
rs11… HTRA1 A AG 1 3.97
rs10… CFH G AG 1 2.43 Complement factor H. Multiple variant SNPs can have additive risk or more significant risk if no
benefit alleles in CFH pathway.
rs49… CFH (Y402H) C CT 1 2.0-11.0 Complement factor H. Vitamin A can INCREASE drusen risk up to 3.27 with variants.
rs22… C3 C GG 0 1.42 Complement component 3.
Benefit SNP
Gene Benefit Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs93… C2 C GG 0 0.46
Complement pathway. Associated with less aggressive complement activation.
rs80… CFB A AG 1 0.50
rs14 CFH G AG 1 0.70 AG0.40 GG
rs42 CT-CFB (SKIV2L)
A AG 1 0.24-0.49 Protective against neovascular (wet AMD)
AMD: Molly
AMD: Genetics-Based Interventions
• Consider increased monitoring in patients over 40 with multiple risk SNPs, including yearly Amsler grid testing or home monitoring system.
• Patients with evidence of macular degeneration should be advised to seek the care of a retinal specialist.
AMD: Genetics-Based Interventions
• Zeaxanthin and Lutein: increase pigment in retinao Alternative to beta-carotene as beta-carotene can heighten risk of lung cancer
in smokers. Vitamin A contraindicated in CFH (Y402H)• Zinc: Down regulates complement pathway• Copper: Balances zinc to prevent copper deficiency neuropathy• AREDS2: Combination of Vitamin C, Vitamin E, zinc, copper, lutein and
zeaxanthin
AMD: Genetics-Based Interventions,Continued
Antioxidants: • Vitamin C: Antioxidant that protects nerves.• Saffron (20mg QD):
o Derived from Crocus sativus flowero Protects against oxidative stress
• Melatonin (3mg QHS):o AMD variants typically have lower melatonin levels.o Protein against retinal pigment epithelial cells from
oxidative damage• Quercetin (typical 250mg QD):
o Protects against oxidative stresso Found in fresh vegetables and fruits
Case Study 4: Coagulation
Coagulation: Genetics Overview
• Individuals with SNPs in their coagulation pathways can have higher risk for DVTs and pulmonary emboli
• Non-genetic DVT risk factors include surgery, hospitalization, pregnancy, birth control pills and long distance travel/immobility
• Many risk alleles relate to:o Platelet pathwayo Thrombin/fibrinogen pathway
Coagulation: Genetics Mechanisms• Factor II (F2) prothrombin: Variants in F2 causes elevated prothrombin levels, which
results in clots with an altered fiber structure. Birth control/HRT confers additive risk.• Factor V (F5): Variants in F5 cause a change in the Factor V Leiden molecule that prevents
protein C from inactivating it. o Factor V is involved in activation of thrombin, thus inactivation results in higher
thrombin levels. Birth control/HRT can activate this cascade.
o This gene alone does not convey high risk but when combined with prothrombin gene mutation can have combined effect.
• Glycoprotein 6 (GP6): Relates to platelet aggregation and stickiness.
Personalized Medicine:Case Study
Daniel: 50 year old male. CAD, migraine, and BPH.
• Family History:o Father: Died of cancero Mother: Hemorrhagic stroke on
warfarin, hyperlipidemia, thyroid disease, MI,
o Brother: Substance abuseo Maternal grandfather: MI
• Medications: Niacin, Curcumasorb,ezetimibe, Vitamin K, andlevothyroxine
RiskSNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs50… F5 Leiden T CC 0 3.57 4-6% of the population carry this gene. 10.3 OR in women with TT allele.
Individuals heterozygous for F5 and F2 have a 20-fold increase in thrombosis risk.
I300… F2 Prothrombin
A GG 0 2.46Even 1 copy of this gene increase risk.
rs22… F11 T CT 1 TT 1.84 TC 1.41
Factor XI.
rs49… ABO T GT 1 1.65 Individuals with these blood types havehigher levels of VWF and Factor VIII.
rs86… PROCR G AG 1 GG 1.81 AG 1.21
Protein C receptor. Activates part ofanticoagulation pathway. EPCR (epithelial
protein C receptor) is another name.
rs18… IL6 C GG 1 1.60 Interleukin 6. Involved in inflammatory pathway.
Benefit SNP
Gene Benefit Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs161 GP6 G AG 1 0.77 GA0.39 GG
Reduces platelet aggregation and recurrentcardiac events.
rs131 CYP4V2 C AG 1 CC 0.69 CA 0.85 Located near prekallikrein.
Coagulation: Daniel
Personalized Medicine:Case Study
Catherine: 66 year old with back pain, hypothyroidism, osteoporosis having surgery. Having surgery for spinal stenosis/spondylolisthesis.
Family history: • Maternal Aunt with history of
blood clot after travel
• Medications: Vitamin D and K, levothyroxine
• Surgeon generally does not generally do DVT prophylaxis other than compression stockings
RiskSNP
Gene Risk Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs50… F5 Leiden T CT 1 3.57 4-6% of the population carry this gene. 10.3 OR in women with TT allele.
Individuals heterozygous for F5 and F2 have a 20-fold increase in thrombosis risk.
I300… F2 Prothrombin
A GG 0 2.46Even 1 copy of this gene increase risk.
rs22… F11 T CT 1 TT 1.84 TC 1.41
Factor XI.
rs49… ABO T GG 0 1.65 Individuals with these blood types havehigher levels of VWF and Factor VIII.
rs86… PROCR G AA 0 GG 1.81 AG 1.21
Protein C receptor. Activates part ofanticoagulation pathway. EPCR (epithelial
protein C receptor) is another name.
rs18… IL6 C GG 0 1.60 Interleukin 6. Involved in inflammatory pathway.
Benefit SNP
Gene Benefit Allele
PatientAllele
Variant (0, 1, 2)
Odds Ratio
Notes
rs161 GP6 G AA 0 0.77 GA0.39 GG
Reduces platelet aggregation and recurrentcardiac events.
rs131 CYP4V2 C AA 0 CC 0.69 CA 0.85 Located near prekallikrein.
Coagulation: Catherine
Coagulation: Genetics-Based Interventions
• Due to the high risk nature of a DVT (up to 10% mortality), results should be confirmed with CLIA approved blood test and hematology consult should be considered for high-risk patients.
• Consider use of compression stockings.
• If patient has SNPs related to F2 prothrombin or F5 leiden, consider anticoagulant use for long-distance travel, surgeries, and other high-risk states.
○ Note: About 20% of population do not properly convert clopidogrel into active agent.
Coagulation: Genetic-based Intervention,Continued
GP6 pathway (which increases platelet aggregation and stickiness, particularly in men) with AA (major alleles so fairly common, G is protection):
• Aspirin therapy may be considered o Shown to significantly benefit individuals with variants who
have had heart attacks 26% reduction in recurrent cardiac events 31% reduction in mortality
Concerns and Regulation related
to Genetic Information
Considerations:
• Considerations before testing: Proper patient counseling• Discuss that their genomics is not their destiny, these are modifiable
risks with actionable items• Understanding what Odds Ratio means and how overall risk
contributes etc. (i.e., 2x risk of something rare or common)• Consent and understanding regarding the following:
• Confirming that patient actually want to know their genomics.• Should genomics go into medical record?• Genomic privacy? Using their real name, using insurance.
Access to Genetic Information
• The Genetics Information Nondiscrimination Act of 2008 (GINA) prohibits insurance companies and employers with >15 employees from acquiring results of genetic tests.
• Group health insurance companies cannot use genetic information to deny coverage, establish pre-existing condition clauses, or change premiums, and may not require genetic testing.
• Genetic information in medical records however are subject to review by providers of life insurance, long-term care insurance, or disability insurance.
Genomic Testing Options for Physicians:
Currently available test options for medical genomics:• Counsyl – Specializes prenatal genetic screening and cancer genetics• Navigenics – Common disease and pharmacogenomics• New Amsterdam – Whole genomic sequencing• Illuminia – Whole genomic sequencing• In-depth DNA – Reports with gene function and interventions
