RESUMO
BACKGROUND: Cytochrome P450 2J2 is mostly expressed in extrahepatic tissues; it metabolizes arachidonic acid to epoxyeicosatrienoic acids, with various cardio protective and anti-inflammatory effects. CYP2J2 polymorphism has been identified as a risk factor for cardiovascular diseases, but its association with psoriasis remains unknown. OBJECTIVE: To evaluate CYP2J2 polymorphism as a risk factor for psoriasis in the Turkish population. METHODS: There were 94 patients with psoriasis and 100 age- and sex-matched healthy controls included in the study. Detailed demographic and clinical characteristics were recorded, and Psoriasis Area and Severity Index (PASI) scores were calculated for psoriasis patients. Venous blood samples were collected from all the participants and CYP2J2 50G>T (rs890293) polymorphism was analyzed using polymerase chain reaction (PCR). RESULTS: Both T allele and TT+GT genotype frequencies were increased in psoriasis vulgaris patients compared to the control group (p=0.024 and p=0.029 respectively, OR=2.82, 95% CI: 1.11-7.15) No association between CYP2J2 polymorphism and clinical features of psoriasis was identified. STUDY LIMITATIONS: A limited number of patients were included in the study. CONCLUSION: CYP2J2 50G>T (rs890293) polymorphism was associated with an increased risk for PsV in the Turkish population.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Polimorfismo Genético , Psoríase/genética , Adulto , Idade de Início , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Citocromo P-450 CYP2J2 , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Estatísticas não Paramétricas , TurquiaRESUMO
STUDY OBJECTIVE: To investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and dose-adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients. DESIGN: Pharmacogenetic analysis of patients enrolled in a previously published study. PATIENTS: One hundred forty-eight adult kidney transplant recipients treated with tacrolimus, enteric-coated mycophenolate sodium, and prednisone for 90 days posttransplantation. MEASUREMENTS AND MAIN RESULTS: ABCC2 c.-24C>T and c.3972C>T, ABCG2 c.421C>A, CYP2C8*3, CYP2J2 c.-76G>T, and UGT2B7 c.372A>G SNPs were determined by real-time polymerase chain reaction. The CYP3A5*3C SNP data were used to eliminate the confounding effect of this variant on the results. ABCC2 c.3972T allele carriers showed higher tacrolimus C:D values than did carriers of the c.3972CC genotype. The CYP2C8*3 variant was also associated with slightly higher tacrolimus C:D values and higher estimated glomerular filtration rate but only in CYP3A5-nonexpressing patients (CYP3A5*3C/*3C carriers). None of the SNPs were associated with mycophenolate sodium dose or episodes of biopsy-confirmed acute rejection or delayed graft function. The CYP2J2 c.-76T allele was associated with increased risk for treatment-induced nausea and/or vomiting (OR: 5.30, 95% confidence interval 1.49-18.79, p<0.05). CONCLUSION: The ABCC2 c.3972C >T polymorphism affected tacrolimus C:D in Brazilian kidney transplant recipients. Further, CYP2C8*3 and CYP2J2 c.-76G>T SNPs influenced the renal function of these patients and the occurrence of adverse events during treatment with tacrolimus and mycophenolate sodium.