Приклади фармакогенетичних варіацій

Acetylation, fast

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Need for higher or more frequent doses of drugs that are acetylated (eg, isoniazid) to produce the desired therapeutic response

Acetylation, slow (drug inactivation by hepatic N-acetyltransferase)

About 50% of the US population

Increased susceptibility to adverse effects of drugs that are acetylated (eg, with isoniazid, peripheral neuritis; with hydralazine or procainamide, lupus)

Aldehyde dehydrogenase-2 deficiency

About 50% of Japanese, Chinese, and other Asian populations

With alcohol ingestion, marked elevations of blood acetaldehyde, causing facial flushing, increased heart rate, diaphoresis, muscle weakness, and sometimes catecholamine-mediated vasodilation with euphoria

CYP2C9 genetic polymorphisms

30% in one study

More common among East Asians

Reduced enzymatic activation of clopidogrel, resulting in reduced antiplatelet effect and increased risk of thrombosis in high-risk patients

G6PD deficiency

10% of males of African descent

Higher prevalence in people of Mediterranean descent

With use of oxidant drugs, such as certain antimalarials (eg, chloroquine, primaquine), increased risk of hemolytic anemia

Genetic polymorphisms of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1)

About 50% of a given population carries at least 1 allele

Increased action of warfarin,* increasing risk of bleeding events

HLA-B*1502

1 to 6/10,000 in countries with mainly white populations

In some Asian countries, about 10 times higher

Increased risk of adverse reactions to carbamazepine, including serious dermatologic reactions (eg, Stevens-Johnson syndrome)

Plasma pseudocholinesterase deficiency

About 1/1500 people

Decreased succinylcholine inactivation

With conventional succinylcholine doses, prolonged paralysis of respiratory muscles and sometimes persistent apnea requiring mechanical ventilation until the drug can be eliminated by alternate pathways