Genetic Markers

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These labs suggest your risk of certain medical conditions based on genetic markers.

Apolipoprotein E Genotype

Apolipoprotein E comes in 3 isoforms: E2, E3, and E4. There is an entire post dedicated to ApoE.

In general, patients with the E4 allele respond less favorably to pharmacologic therapy with statins. Simvastatin has evidence of preferred efficacy over other statins for patients with E4 alleles.

We test for this because it gives us more information about your risk for cardiovascular disease and helps us determine how aggressive we need to be with our interventions.

Goal – decrease risk for atherosclerosis and Alzheimer’s Disease.

What to do to improve it – As stated many times, the best thing is to improve overall health to the greatest extent possible.

Cyp2C19 (*2*3)

The Cytochrome P450 (CYP450) pathway is a series of enzymes in the liver that convert &/or detoxify medications and hormones. CYP2C19 is one of these enzymes. There are a few different ‘versions’ of this enzyme that are encoded by individual genes.

Type 1/1 expresses optimal activity of this enzyme and allows normal metabolism. Types 2 & 3 show a decreased level of activity. Type 17 expresses an increased level of activity.

Several medications are metabolized through this enzyme. Plavix is one of those medications. Plavix (clopidigrel) is a pro-drug meaning that it must be converted by this enzyme into its active form. Therefore, if an individual is taking Plavix and has anything other than 1/1 then their dose may need to be increased to allow for optimal blood levels of the active form of Plavix.

What to do to improve it – adjust doses of medications if indicated.

The following medications are known to be processed by CYP2C19 and may require a dosage adjustment

  • Clopidogrel (Plavix)
  • Amitriptyline (Elavil)
  • Citalopram (Celexa)
  • Clomipramine
  • Diazepam (Valium)
  • Escitalopram (Lexapro)
  • Imipramine (Tofranil)
  • Sertraline (Zoloft)
  • Phenytoin (Dilantin)
  • Lansoprazole (Prevacid)
  • Omeprazole (Prilosec)
  • Carisoprodol
  • Propranolol
  • Voriconazole

Goal – 1/1

What to do to improve it – adjust medication doses as needed

CYP2C19 (*17)

When a patient has CYP2C19 *17 variant the activity of this enzyme is increased and may require medication dose adjustments if they are taking the medications listed above.

Goal – 1/1

What to do to improve it – adjust medications accordingly

Factor V Leiden

Factor V Leiden (FVL) is a genetically acquired trait and a variant of the protein Factor V. Individuals with FVL have a hypercoagulable state. FVL mutation may be heterozygous (Arg/Gln) with one copy of the changed gene or homozygous (Gln/Gln) with two copies of the changed gene. Arg & Gln are symbols for the Amino Acids on the FVL protein. Arg is the normal amino acid and is replaced by Glycine (Gly) in the abnormal FVL protein. It is the Glycine replacement that makes Factor V resistant to inactivation by Protein C in the coagulation cascade and increases the risks of clotting. The abnormal clotting nearly always occurs in veins.

There is an 80-100x increased risk of Venous Thromboembolic Events (VTE) in patients with compound heterozygosity for FVL (Arg/Gly) and Prothrombin G20210A Mutation.

Goal – reduce risk of clotting by maximizing other risk factors

What to do to improve it – Exercise, estrogen management, smoking cessation, avoid prolonged sitting, adequate rehydration, advise surgeons prior to any procedure, possibly discontinue hormone replacement therapy, frequently elevate feet. Ensure adequate intake of Omega-3s.

Prothrombin Mutation

The prothrombin mutation results from an alteration in the 3′-untranslated region of the prothrombin gene. It is associated with increased risk of developing VTE. The ‘G’ and ‘A’ refer to the nucleotides guanine & adenine in the DNA which make up the gene at position 20210. Hence the name “Prothrombin G20210 Mutation.”

Goal – G/G

What to do to improve it – decrease controllable risk for blood clots as stated above.

MTHFR

MTHFR stands for MethyleneTetraHydroFolate Reductase and is the rate limiting enzyme in the methylation pathway. This enzyme is encoded by the MTHFR gene. The methylation pathway (or cycle) is responsible for the remethylation of homocysteine to methionine. MTHFR activity is inhibited by the binding of dihydrofolate (DHT) and S-adenosylemethionine (SAM).

The MTHFR gene can encode for 2 different proteins. 1 is the C form (normal form) and the other is the T form (thermolabile form). Patients who are homozygous (they have both the same) for T/T it indicates that the enzyme does not effectively metabolize folic acid (folate) into its active form, methylfolate (5-MTHF). Patients homozygous for T/T are at increased risk for elevated homocysteine (see below). They also will not generally respond well to supplementation with folic acid and should take the active form, 5-MTHF.

Goal – C/C.

What to do to improve it – We can’t change the genetics but we can minimize the impact. Take methylcobalamin & 5-MTHF (methylated B12 & folic acid). If you still have problems after methylcobalamin & 5-MTHF then you may have a methylation pathway problem that needs further assessment and interventions.

Read our post on MTHFR & methylation for more information.