Cytochrome P450 2C19

Cytochrome P450 2C19 or Cytochrome P450 Family 2 Subfamily C Member 19 or CYP2C19 is a gene linked to drug metabolism. Variants in CYP2C19 or lack of the gene are extremely common, with one study finding that over 50% of people in the study had either no CYP2C19 gene or a variant of it.

Function
Variants in CYP2C19 or the absence of the gene can significantly alter the drug metabolism of several medications, genotype‐based dosing guidelines available for these medications.

Drug responses
CYP2C19 variants are known to affect the metabolism of the tricyclic antidepressants amitriptyline, clomipramine, doxepin and imipramine, the selective serotonin reuptake inhibitors (SSRIs) citalopram and sertraline, the antifungal drug voriconazole, and the antiplatelet agent clopidogrel which reduces blood clotting.

An FDA warning was been added to clopidogrel in 2009 which started that genetic testing was available to determine if a patient could be a poor metabolizer, and that this would make the drug less effective.

Variants

 * rs12248560 (CYP2C19*17) ultrarapid CYP2C19 metabolism and increases increases enzyme function, acting in the opposite way to rs4244285. In Europe, this variant affects between 1 in 3 and 1 in 9 people.
 * rs4244285 (CYP2C19*2) is the most common variant in Caucasians, and results in aberrant splicing and loss of function, rs12248560 acts in the opposite way. This variant also affects around 1 in 5 people in the Romany (traveler) community in one study. If combined with the CYP2C19*1 normal functioning variant drug effectiveness improves compared to having two copies of rs4244285.
 * (CYP2C19*1) normal functioning
 * rs17885098 (CYP2C19*1B) normal function
 * rs3758581 (CYP2C19*1C, CYP2C19*3C, CYP2C19*4A, CYP2C19*4B and many others) 991A>G normal functioning, some others cause loss of function
 * rs4986893 (CYP2C19*3, CYP2C19*3A, CYP2C19*3B, CYP2C19*3C 636 G>A)
 * rs3758581 (CYP2C19*3A) loss of function
 * rs17886522 (CYP2C19*3B or CYP2C19*20) loss of function
 * rs3758581 (CYP2C19*3B or CYP2C19*20, CYP2C19*3C) loss of function
 * rs144036596 (CYP2C19*3B or CYP2C19*20) loss of function
 * rs4986893 (CYP2C19*3B or CYP2C19*20) loss of function
 * rs397516695 (CYP2C19*3C) 407T>A
 * rs17886522 (CYP2C19*3C) 1251A>C
 * rs28399504 (CYP2C19*4) A>G
 * rs unknown (CYP2C19*5) 1297 C>T
 * rs unknown (CYP2C19*6)

Conflicting data in different studies make it unclear which areas of European are most affected by these variants.

CYP2D6
Common variants of cytochrome P450 2D6 (CYP2D6) also impact the effects of these drugs.

ME/CFS
No particular link to ME/CFS has been found for people with CYP2C19 gene variants. One study found CYP2C19 to be one of a number of genes associated with multiple chemical sensitivity, but other studies failed to find this.

Learn more

 * CYP2C19 - Gene cards
 * CYP2C19 variants - PharmVar archive