It Is Not Always Alcohol Abuse--A Transferrin Variant Impairing the CDT Test
| Autor: | Yoshinao Wada, Christoph Seger, Marianne Grüneberg, Julien H. Park, Ingrid DuChesne, Michael Said, Andrea Zühlsdorf, Stephan Rust, Janine Reunert, Thorsten Marquardt |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Spectrometry Mass Electrospray Ionization Glycosylation Alcohol abuse Bioinformatics medicine.disease_cause 01 natural sciences 03 medical and health sciences chemistry.chemical_compound symbols.namesake medicine Humans Chromatography High Pressure Liquid chemistry.chemical_classification Sanger sequencing Mutation business.industry Isoelectric focusing 010401 analytical chemistry Alcohol dependence Transferrin Genetic Variation General Medicine medicine.disease Molecular biology 0104 chemical sciences Alcoholism 030104 developmental biology chemistry symbols Biomarker (medicine) business Biomarkers |
| Zdroj: | Alcohol and alcoholism (Oxford, Oxfordshire). 51(2) |
| ISSN: | 1464-3502 |
| Popis: | Aims Elevated Carbohydrate-deficient transferrin (CDT) levels are used as a biomarker in order to screen for chronic alcohol abuse. Transferrin (Tf) variants can impair methods to measure elevated CDT levels such as high-performance liquid chromatography (HPLC). We present a Tf variant affecting the second glycosylation site of Tf and the complications it causes in diagnosing alcoholism. Methods A blood sample from a patient with suspected alcohol abuse was analyzed with HPLC, isoelectric focusing, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), immunoprecipitation and SDS-Page. Sanger sequencing of Tf was performed to detect Tf mutations. Results HPLC, SDS-Page and IEF showed a distinctly increased disialo-Tf fraction while the tetrasialo-Tf fraction was decreased, ESI-TOF-MS confirmed these results. Sanger sequencing revealed the Tf mutation c.1889 A>C, deleting a Tf glycosylations site and thereby causing elevated disialo-Tf levels. Conclusions Transferrin mutations can severely impair the diagnostics of chronic alcohol abuse by causing false positive results. This has to be considered when CDT screening is used to detect alcoholism. |
| Databáze: | OpenAIRE |
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