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Acetylator phenotype in Behçet's disease
Rafid A Najim1, Khalifa E Sharquie, Mahmood H Al-Janabi
1Department of Pharmacology, College of Medicine, University of Baghdad, Baghdad, Iraq.
Insights
Behçet's disease (BD) patients exhibit a unique acetylator status, with a higher prevalence of slow or non-acetylators compared to healthy individuals. This acetylator status is linked to disease severity and HLA-B51 positivity.
Area of Science:
- Pharmacogenomics
- Immunology
- Rheumatology
Background:
- Behçet's disease (BD) is a complex inflammatory disorder with unclear pathogenesis.
- Acetylation status, determined by drug metabolism, is known to vary among individuals.
- Genetic factors, such as HLA-B51, are associated with BD susceptibility.
Purpose of the Study:
- To investigate the acetylator status in patients with Behçet's disease.
- To compare the acetylator status of BD patients with that of healthy individuals.
- To explore the relationship between acetylator status, disease severity, and HLA-B51 in BD.
Main Methods:
- A case-control study involving 41 BD patients and 37 healthy controls.
- Oral administration of dapsone (100 mg) followed by plasma dapsone and monoacetyldapsone level determination via HPLC after 3 hours.
- Assessment of HLA-B51, Clinical Manifestation Index (C.M.I.), and pathergy test in BD patients.
Main Results:
- Healthy individuals showed 70.2% slow acetylators and 29.8% rapid acetylators.
- BD patients exhibited 53.7% slow acetylators and 46.3% non-acetylators; no rapid acetylators were observed.
- A significant negative association was found between slow/non-acetylator status and BD severity, with slow acetylators having more severe disease.
- BD patients positive for HLA-B51 predominantly displayed slow or non-acetylator status.
Conclusions:
- Behçet's disease patients possess a distinct acetylator phenotype.
- Acetylation status appears to be a significant factor influencing BD pathogenesis and clinical presentation.
- These findings may inform future therapeutic strategies and understanding of BD etiology.
Abstract:
The purpose of this study was to determine the acetylator status in Behçet's disease (BD) patients and compare it to a matched group of normal individuals. Thirty-seven healthy volunteers and forty-one BD patients were included. Detailed history was taken from the patients. HLA-B51 was determined in the BD patients. In addition, the Clinical Manifestation Index (C.M.I.) was determined for each patient. Pathergy test was also done. After an overnight fast, each control subject and patient received a single oral dose of 100 mg of DDS. A blood sample was collected after 3 hours and the plasma was separated for determination of dapsone/monoacetyldapsone by HPLC. The frequency of slow acetylators in healthy individuals was 70.2%, while the frequency of rapid acetylators was 29.8%. The frequency of slow acetylators in BD patients was 53.7%, while the frequency of non-acetylators (undetected monoacetyldapsone MADDS in plasma) was 46.3%. There were no rapid acetylators among the BD patients. There was a strong negative association between the acetylator status and the severity of BD. In addition, acetylator status correlated with HLA-B51, in that BD patients with positive HLA-B51 were characterized by a very slow or non-acetylator status. Slow or non-acetylators had more severe BD. We conclude that BD patients have a unique acetylator status. This finding may have implications for the theories for the pathogenesis of the disease as well as for therapeutic aspects.