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Editor's Correspondence
November 25, 2002

Ethnic, Racial, and Sex-Specific Factors Are Important in Cardiovascular Pharmacotherapeutics

Arch Intern Med. 2002;162(21):2494. doi:

In recent years, attention has been focused on genetic polymorphisms as reported recently by Flockhart and Tanus-Santos.1 However, ethnic, racial, and sex-specific genetic factors may also lead to differences in cardiovascular pharmacotherapeutics and are not acknowledged in their current review.

Racial differences in CYP2D6 have been documented, which are also not included in the review by Flockhart and Tanus-Santos. CYP2D6 oxidizes several β-receptor antagonists, most notably metoprolol.2 Many CYP2D6 polymorphisms, conferring phenotypic differences in enzyme function, have been reported. Patients are described as extensive or poor metabolizers. Most alleles identified cause a loss of function or decreased function. Poor metabolizer phenotypes have been estimated at 1% in Chinese subjects compared with 7% in white subjects.3 During long-term oral administration of metoprolol to Chinese patients with poor metabolizer genotype CYP2D6 *10A, subjects demonstrated higher steady state level of metoprolol racemates.3 Some authors suggest that the poor metabolizer prevalence is why Asians and possibly whites may require lower doses of metoprolol for a significant clinical response. Other alleles lead to an increased metabolic activity by gene duplication described as an ultrarapid metabolizer phenotype. Gene duplication has been observed in Saudi Arabians and Ethiopians.4

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