Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema.

Pharmacogenetics and Genomics
A Woodard-GriceN J Brown

Abstract

Angioedema is a rare adverse effect of angiotensin-converting enzyme (ACE) inhibitors, which occurs more commonly in women and black Americans. Angioedema is thought to result from decreased degradation of vasoactive peptides. During ACE inhibition, bradykinin is primarily inactivated by aminopeptidase P (APP). Earlier studies have provided conflicting data with regard to serum APP activity in patients with a history of ACE inhibitor-associated angioedema. A single nucleotide polymorphism, -2399C>A (rs3788853, C-2399A), in XPNPEP2, the X-linked gene that encodes membranous APP, has been reported to associate with APP activity. To test the hypothesis that the relationship between XPNPEP2 C-2399A genotype and APP activity or ACE inhibitor-associated angioedema is sex-dependent and race-dependent. We compared C-2399A genotype frequencies in 169 cases with a history of ACE inhibitor-associated angioedema and 397 ACE inhibitor-exposed controls. Controls were prespecified to be 50% white, 50% black, and 50% women. Cases and controls were group matched for age and smoking. XPNPEP2 C-2399A genotype associated with serum APP activity in both men and women. Serum APP activity was lower in men than in women, independent of genotype. XPNPE...Continue Reading

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