title: Genetic determinants of metamizole metabolism modify the risk of developing anaphylaxis.
abstract: Metamizole is a NSAID that has been banned in several countries because of its toxicity. It is often involved in selective hypersensitivity reactions and most hypersensitivity patients develop anaphylaxis. Metamizole is rapidly metabolized, and metabolic profiles are related to genetic factors. We analyzed whether genetic determinants of metamizole metabolism influence the risk of developing hypersensitivity in 265 patients diagnosed with hypersensitivity to metamizole and 362 healthy individuals who tolerated metamizole. Slow acetylation is associated with an increased risk of developing selective hypersensitivity to metamizole [odds ratio for slow alleles=2.17 (95% confidence interval=1.44-3.27); P=0.00016], and particularly anaphylaxis [odds ratio=4.77 (95% confidence interval=2.28-9.98); P=0.000006], with a significant gene-dose effect. The association was not identified in patients with cross-hypersensitivity. Cytochrome P450 2C9 (CYP2C9) and cytochrome P450 2C19 (CYP2C19) genotypes did not influence risk association. Our findings raise the hypothesis of genetically determined metabolic variability as a risk factor for developing anaphylaxis with metamizole.
authors.affiliation: aDepartment of Pharmacology, University of Extremadura, Cáceres bAllergy Service, Hospital Infanta Leonor, Madrid cAllergy Service, Hospital Infanta Cristina, Badajoz dAllergy Service, Carlos Haya Hospital, Málaga eAllergy Service, Hospital de Mérida, Mérida, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: Gara
authors.initials: G
authors.lastname: Esguevillas
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-López
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Menaya
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.forename: Gemma
authors.initials: G
authors.lastname: Amo
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canto
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Concepción
authors.initials: C
authors.lastname: Cordobés
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000707:Anaphylaxis / Q000139:chemically induced* / Q000235:genetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D004177:Dipyrone / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19