Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection
| العنوان: | Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection |
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| المؤلفون: | F, Girardin, Y, Daali, M, Gex-Fabry, M, Rebsamen, P, Roux-Lombard, A, Cerny, F, Bihl, J, Binek, D, Moradpour, F, Negro, J, Desmeules, Gieri, Cathomas |
| المصدر: | Journal of Viral Hepatitis, Vol. 19, No 8 (2012) pp. 568-73 |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | ddc:616, Adult, Male, Dextromethorphan/metabolism, ddc:617, Dextrorphan, Genotype, ddc:616.07, Hepatitis C, Chronic, Middle Aged, digestive system, Dextromethorphan, Cohort Studies, ddc:616.89, Cytochrome P-450 CYP2D6, Cytochrome P-450 CYP2D6/genetics/metabolism, Humans, Hepatitis C, Chronic/pathology, Female, skin and connective tissue diseases, Autoantibodies/immunology, Switzerland, Dextrorphan/metabolism, Aged, Autoantibodies |
| الوصف: | Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM-1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM-1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with the CYP2D6 genotype in most LKM-negative patients, whereas only three LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was sixfold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, P = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies. In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies. |
| تدمد: | 1365-2893 1352-0504 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::05b4e5227de1bdbccc61de31542db0a6 https://pubmed.ncbi.nlm.nih.gov/22762141 |
| Rights: | RESTRICTED |
| رقم الانضمام: | edsair.pmid.dedup....05b4e5227de1bdbccc61de31542db0a6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652893 13520504 |
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