CYP2C9, CYP2D6, G6PD, GCLC, GSTM1 and NAT2 gene polymorphisms and risk of adverse reactions to sulfamethoxazole and ciprofloxacin in San Luis Potosí, Mexico

• Published in: Meta Gene Vol. 21; p. 100574
• Main Authors: Hernández-Verdin, Eduardo, Ganelón-Ríos, Andrea, Pettet-Ruiz, Guillermo, Sánchez-Garza, Mireya, Reinoso-Reyes, Joaquín, López-Revilla, Rubén
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2019
• Subjects: Allele variants; Ciprofloxacin; CYP2C9; CYP2D6; G6PD; GCLC; GSTM1; Hemolytic anemia; Hypersensitivity; NAT2; Pharmacogenetics; Single nucleotide polymorphisms; Sulfamethoxazole; Pharmacogenetics; G6PD; GSTM1; Hypersensitivity; CYP2C9; Sulfamethoxazole; GCLC; Hemolytic anemia; CYP2D6; NAT2; Allele variants; Single nucleotide polymorphisms; Ciprofloxacin
• ISSN: 2214-5400; 2214-5400
• DOI: 10.1016/j.mgene.2019.100574

Sulfamethoxazole (SMX) and ciprofloxacin (CPFX), two of the most prescribed antimicrobials worldwide, induce adverse reactions (ADRs) determined by clinically relevant variants of the CYP2C9, CYP2D6, G6PD, GCLC, GSTM1, and NAT2 genes. We designed methods to generate and sequence amplification products to identify the relevant single nucleotide polymorphisms (SNPs) in 100 San Luis Potosí City residents. Twenty-seven of the 43 SNPs selected were found and the following phenotype frequencies were inferred: CYP2C9 normal 73%, intermediate 25%, poor 2%; CYP2D6 normal 11%, intermediate 2%, poor 6%, undetermined 81%; GCLC mRNA expression normal 13%, intermediate 52%, low 33%; NAT2 acetylator rapid 19%, intermediate 50%, poor 31%; GSTM1 normal 52%, poor 48%. Five of the 12 haplotypes detected were in complete linkage disequilibrium. The following variants were identified for the first time in Mexicans: CYP2C9*26, *44, *45, *55; CYP2D6 rs1135824, *6B, *50, *90; GCLC rs761142. Ten-percent of the sampled subjects appears to be at maximum risk of SMX hypersensitivity since they have concomitant low GCLC mRNA expression/normal CYP2C9/poor NAT2/poor GSTM1 phenotypes. Ten-percent of the men carrying the G6PD-Canton variant in hemizygous state and the GCLC rs761142 variant in the homozygous state may be at risk of hemolytic anemia by SMX. Since the G6PD-Mediterranean variant was not detected, the group included is not at risk of hemolytic anemia by CPFX. Eighty-nine percent of the subjects carry the CYP2D6 rs1135824 variant in the homozygous or heterozygous state but their risk of ADRs to CPFX is undetermined because the activity of the variant enzyme is unknown.