Genetics Testing - Pharmacogenomics

Pharmacogenomics

Advanta Analytical Laboratories provides Pharmacogenomics testing and interpretive services to physicians, clinics and hospitals that want to bring the benefits of Pharmacogenetics screening to their patients.

General Information

The effects of most medications are dependent on any specific medication being metabolized in the body. That metabolism is a result of the action of enzymes. Enzymes are proteins that are coded in the individual’s DNA. Most medications are metabolized in multiple steps performed by various enzymes coded by multiple genes located along different segments of the DNA, often on multiple chromosomes. The largest group of enzymes responsible for the metabolism of all drugs is found in the Cytochrome P450 system.

The Cytochrome P450 system consists of more than 50 enzymes of which six are principle enzymes in the metabolism of more than 90% of all drugs. These are coded for the genes CYP2D6, CYP3A4, CYP1A2, CYP2C9, CYP2C19 and CYP3A5, the first two being the two most significant of these.
Genetic variability or Polymorphisms in any of these genes can influence how a patient will respond to any given drug or class of drugs. The gene for any one enzyme may contain one or more polymorphisms or SNiPs , each of which may increase the rate of the enzymatic reaction, decrease the rate of reaction or not affect the enzyme reaction. These effects correspond respectively to what are termed hypermetabolizers, poor metabolizers and wild type ("normal") metabolizers.

Compounding this is the fact that some drugs are active as they are administered, such as propranolol and ibuprofen. Other drugs, such as codeine and hydrocodone, are inactive as taken and must be metabolized by an enzyme (CYP2D6 in the case of codeine) to an active metabolite to have the intended physiologic effect. For this reason, these drugs are referred to as Prodrugs.

The raw data produced by pharmacogenetic (PGx) testing can be quite cryptic and puzzling. For this reason, Advanta Analytical Laboratories, with the input from expert consultants, will furnish you as intuitive and as useful reports as possible. Our reports will give you an assessment of any risk factors as well as a review of your patient’s PGx testing and how the metabolism of many drugs and drug classes will be affected. You will receive a list of medications with which you should expect normal or abnormal metabolism, a list of medications where you might consider altering the normal dosing and a list of any drugs for which you should consider using an alternative agent because of concerns for either safety or toxicity. It is quite likely that ALL patients have at least some significant polymorphisms.

Advanta Drug Sensitivity Panel

While we test individual genes, the real benefit of pharmacogenomics lies in the interplay between multiple genes and multiple drugs. Advanta's drug sensitivity panel identifies patients susceptible to adverse events and red-flags drug interactions that complicate the patient's care.

Pharmacogenomic testing: Relevance in medical practice

CURRENT PANELS AVAILABLE.

TESTING REFERENCE
NOTE: The summaries below are meant for basic informational purposes only. It is not intended to serve as medical advice, substitute for a doctor's appointment or to be used for diagnosing or treating a disease.
GENE TEST SUITE
GENE PANEL PANEL DESCRIPTION
CYP2C9

The Cytochrome P450 2C9 (CYP2C9) is involved in the metabolism of 15% of clinically important medications including various Psychotropics, Nonsteroidal Anti-Inflammatory Drugs (NSAIDS), and Hypoglycemics, among others. This enzyme is highly polymorphic and to date, 30 different variant alleles have been identified.

The CYP2C9 assay identifies some common variants that are associated variability in CY2C19 enzyme activity, which has important pharmacological and toxicological implications for anticonvulsants and certain antidepressants.

VKORC1

VKORC1 enzyme is primarily responsible for the metabolism of the person's vitamin K intake. Mutations in this gene can be associated with deficiencies in vitamin-K-dependent clotting factors. The product of this gene encodes the enzyme that is responsible for reducing vitamin K 2,3-epoxide to the enzymatically activated form. Fatal bleeding can be caused by vitamin K deficiency and by the vitamin K antagonist warfarin, and it is the product of this gene that is sensitive to warfarin.

CYP2C19

The Cytochrome P450 2C19 (CYP2C19) is involved in the metabolism of 10% of clinically important medications including various Psychotropics, Anti-convulsants and Proton Pump Inhibitors (PPis), among others.

This enzyme is highly polymorphic and more than 30 different variant alleles have been identified. The CYP2C19 assay identifies some common variants that are associated variability in CY2C19 enzyme activity, which has important pharmacological and toxicological implications for antidepressants and some benzodiazepines.

CYP2D6

The Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of 25% of clinically important medications including various Psychotropics, Analgesics, and Beta-blockers, among others. This enzyme is highly polymorphic and more than 100 different variant alleles have been identified.

The CYP2D6 assay identifies some common variants that are associated variability in CYP2D6 enzyme activity, which has important pharmacological and toxicological implications for antidepressants and antipsychotics.

CYP3A4

The Cytochrome P450 3A4 and 3A5 (CYP3A4 and CYP3A5) account for 4D-80% of total CYP in human liver and intestine, respectively. Most importantly,CYP3A enzymes metabolize 50% of commonly used drugs including various Statins, Antibiotics/anti-virals, and Analgesics, among others.

CYP3A4 and CYP3A5 enzymes have overlapping substrate specificity and the contribution of CYP3A5 in the overall metabolism is smaller than the one for CYP3A4. The overall CYP3A metabolism status is expected to affect drug that have a narrow therapeutic index.

CYP3A5

The Cytochrome P450 3A4 and 3A5 (CYP3A4 and CYP3AS) account for 4D-80% of total CYP in human liver and intestine, respectively. Most importantly, CYP3A enzymes metabolize 5O% of commonly used drugs including various Statins, Antibiotics/anti-virals, and Analgesics, among others.

CYP3A4 and CYP3A5 enzymes have overlapping substrate specificity and the contribution of CYP3A5 in the overall metabolism is smaller than the one for CYP3M. The overall CYP3A metabolism status is expected to affect drugs that have a narrow therapeutic index.

Factor II -V MTHFR

Factor II Prothrombin and Factor V Leiden gene variations are the two most common causes of inherited thrombophilia. Methylenetetrahydrofolate Reductase (MTHFR) gene mutations are strongly associated with hyperhomocysteinemia, which increases cardiovascular disease risk.

These markers provide important information when designing anti-coagulant therapy.

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AMYTRIPTYLINE PANEL
GENE PANEL CPT PANEL DESCRIPTION
CYP2D6 81226 CYP2D6 GENE ANALYSIS COMMON VARIANTS
DIAGNOSIS (ICD-10) Diagnosis Description
F31.30Bipolar disorder, current episode depressed, mild or moderate severity, unspecified
F31.31Bipolar disorder, current episode depressed, mild
F31.32Bipolar disorder, current episode depressed, moderate
F31.4Bipolar disorder, current episode depressed, severe, without psychotic features
F31.5Bipolar disorder, current episode depressed, severe, with psychotic features
F31.60Bipolar disorder, current episode mixed, unspecified
F31.61Bipolar disorder, current episode mixed, mild
F31.62Bipolar disorder, current episode mixed, moderate
F31.63Bipolar disorder, current episode mixed, severe, without psychotic features
F31.64Bipolar disorder, current episode mixed, severe, with psychotic features
F31.75Bipolar disorder, in partial remission, most recent episode depressed
F31.76Bipolar disorder, in full remission, most recent episode depressed
F31.77Bipolar disorder, in partial remission, most recent episode mixed
F31.78Bipolar disorder, in full remission, most recent episode mixed
F32.9Major depressive disorder, single episode, unspecified
F33.0Major depressive disorder, recurrent, mild
F33.1Major depressive disorder, recurrent, moderate
F33.2Major depressive disorder, recurrent severe without psychotic features
F33.3Major depressive disorder, recurrent, severe with psychotic symptoms
F33.40Major depressive disorder, recurrent, in remission, unspecified
F33.41Major depressive disorder, recurrent, in partial remission
F33.42Major depressive disorder, recurrent, in full remission
F33.9Major depressive disorder, recurrent, unspecified
G10Huntington's disease
E75.22Gaucher disease Type 1

Letter of Medical Necessity

Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants

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PLAVIX (CLOPIDOGREL) PANEL
GENE PANEL CPT PANEL DESCRIPTION
CYP2C19 81225 CYP2C19 GENE ANALYSIS COMMON VARIANTS
DIAGNOSIS (ICD-10) Diagnosis Description
Z79.02Long term (current) use of antithrombotics/antiplatelets (MUST INCLUDE AS SECONDARY DX)
I25.10Atherosclerotic heart disease of native coronary artery without angina pectoris
I25.110Atherosclerotic heart disease of native coronary artery with unstable angina pectoris
I25.111Atherosclerotic heart disease of native coronary artery with angina pectoris with documented spasm
I25.118 Atherosclerotic heart disease of native coronary artery with other forms of angina pectoris
125.5Ischemic cardiomyopathy
125.6Silent myocardial ischemia
125.720Atherosclerosis of autologous artery coronary artery bypass graft(s) with unstable angina pectoris
125.721Atherosclerosis of autologous artery coronary artery bypass graft(s) with angina pectoris with documented spasm
125.728Atherosclerosis of autologous artery coronary artery bypass graft(s) with other forms of angina pectoris
125.760Atherosclerosis of bypass graft of coronary artery of transplanted heart with unstable angina
125.761Atherosclerosis of bypass graft of coronary artery of transplanted heart with angina pectoris with documented spasm
125.768Atherosclerosis of bypass graft of coronary artery of transplanted heart with other forms of angina pectoris
125.790Atherosclerosis of other coronary artery bypass graft(s) with unstable angina pectoris
125.791Atherosclerosis of other coronary artery bypass graft(s) with angina pectoris with documented spasm
125.798Atherosclerosis of other coronary artery bypass graft(s) with other forms of angina pectoris
125.810Atherosclerosis of coronary artery bypass graft(s) without angina pectoris
125.812Atherosclerosis of bypass graft of coronary artery of transplanted heart without angina pectoris
125.84Coronary atherosclerosis due to calcified coronary lesion
125.83Coronary atherosclerosis due to lipid rich plaque
125.89Other forms of chronic ischemic heart disease
125.9Chronic ischemic heart disease, unspecified
163.511Cerebral infarction due to unspecified occlusion or stenosis of right middle cerebral artery
163.512Cerebral infarction due to unspecified occlusion or stenosis of left middle cerebral artery
163.519Cerebral infarction due to unspecified occlusion or stenosis of unspecified middle cerebral artery
163.59Cerebral infarction due to unspecified occlusion or stenosis of other cerebral artery
166.01Occlusion and stenosis of right middle cerebral artery
166.02Occlusion and stenosis of left middle cerebral artery
166.03Occlusion and stenosis of bilateral middle cerebral arteries
166.8Occlusion and stenosis of other cerebral arteries
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COMPREHENSIVE PANEL
GENE PANEL CPT PANEL DESCRIPTION
CYP2C19 81225 CYP2C19 GENE ANALYSIS COMMON VARIANTS
CYP2C9 81227 CYP2C9 GENE ANALYSIS COMMON VARIANTS
CYP2D6 81226 CYP2D6 GENE ANALYSIS COMMON VARIANTS
CYP3A4 81401 MOLECULAR PATH PROC-LVL 2-CMN VAR
CYP3A5 81401A MOLECULAR PATH PROC-LVL 2-CMN VAR
VKORC1 81355 GENE ANALYSIS COMMON VARIANTS
F2 81240 F2 GENE ANALYSIS 2021OG.A>VARIANT
F5 81241 F5 GENE ANALYSIS LEIDEN VARIANT
MTHFR 81291 MTHFR GENE ANALYSIS COMMON VARIANTS
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CARDIOLOGY PANEL
GENE PANEL CPT PANEL DESCRIPTION
CYP2C19 81225 CYP2C19 GENE ANALYSIS COMMON VARIANTS
CYP2C9 81227 CYP2C9 GENE ANALYSIS COMMON VARIANTS
CYP2D6 81226 CYP2D6 GENE ANALYSIS COMMON VARIANTS
CYP3A4 81401 MOLECULAR PATH PROC-LVL 2-CYP3A4 CMN VAR
CYP3A5 81401A MOLECULAR PATH PROC-LVL 2-CYP3A5 CMN VAR
VKORC1 81355 VKORC1 GENE ANALYSIS COMMON VARIANTS
F2 81240 F2 GENE ANALYSIS 2021OG.A>VARIANT
F5 81241 F5 GENE ANALYSIS LEIDEN VARIANT
MTHFR 81291 MTHFR GENE ANALYSIS COMMON VARIANTS
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PAIN MANAGEMENT PANEL
GENE PANEL CPT PANEL DESCRIPTION
CYP2C19 81225 CYP2C19 GENE ANALYSIS COMMON VARIANTS
CYP2C9 81227 CYP2C9 GENE ANALYSIS COMMON VARIANTS
CYP2D6 81226 CYP2D6 GENE ANALYSIS COMMON VARIANTS
CYP3A4 81401 MOLECULAR PATH PROC-LVL 2-CMN VAR
CYP3A5 81401A MOLECULAR PATH PROC-LVL 2-CMN VAR
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PSYCHIATRIC PANEL
GENE PANEL CPT PANEL DESCRIPTION
CYP2C19 81225 CYP2C19 GENE ANALYSIS COMMON VARIANTS
CYP2C9 81227 CYP2C9 GENE ANALYSIS COMMON VARIANTS
CYP2D6 81226 CYP2D6 GENE ANALYSIS COMMON VARIANTS
CYP3A4 81401 MOLECULAR PATH PROC-LVL 2-CMN VAR
CYP3A5 81401A MOLECULAR PATH PROC-LVL 2-CMN VAR
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