Sialic acid : A new potential marker of alcohol abuse

University dissertation from Stockholm : Karolinska Institutet, Department of Clinical Neuroscience

Abstract: Biological markers have been used for several years to detect heavy alcohol consumption or organ damage induced by alcohol. Early identification of alcohol abuse or alcohol dependence could increase the likelihood of early treatment, thereby reducing health damage and health care costs. Self- reported alcohol consumption is an important diagnostic instrument, but objective screening tools such as biological markers are also needed. The aim of the present thesis was to investigate serum sialic acid (SA) as a potential marker for excessive alcohol consumption and make a preliminary clinical evaluation, including measurement of changes of SA levels in saliva and urine. In addition, factors, which may influence serum SA concentrations in a healthy population, were analysed. Furthermore, a preliminary method was developed for the visualisation and quantification of SA on peripheral blood cells. Serum and saliva concentrations of SA were significantly higher among alcohol dependent patients with excessive alcohol consumption as compared to social drinkers both female and male. The levels in urine were not affected. In addition, serum SA levels decreased significantly during treatment and abstinence from alcohol. Serum SA was also significantly increased directly after a relapse as compared to the level after four weeks or more of abstinence, suggesting that serum SA could be used as a marker for excessive alcohol consumption and a useful tool to monitor treatment. The patients' amount and patterns of alcohol intake differed considerably during their relapses, indicating that serum SA may be sensitive to even a brief relapse. In a healthy population, serum SA concentrations are relatively stable with age, especially in men. Among women there was a tendency towards increasing levels after menopause. The SA concentrations showed a significant positive association with body mass index, systolic and diastolic blood pressure both among women and men. Smoking was associated with increased serum SA levels in men but not in women. For women, SA correlated significantly with the use of contraceptive pills. Insight into the impact of different factors other than alcohol, which influence the level of the marker, can assist in the interpretation of the SA results. This study also presents a method for the study of SA in peripheral blood cells using conventional fluorescence microscopy and confocal microscopy. Lectins with specificity for SA were used. The results show specific binding to the surface of erythrocytes with all of the lectins used. Surface and intracellular glycoconjugates were visualised in granulocytes, eosinophils and neutrophils. In lymphocytes, the labelling was seen clearly on the surface but the intracellular labelling was more diffuse. The method is a novel approach to visualise and quantify surface and intracellular SA on peripheral blood cell. In summary, serum and saliva SA concentrations are affected by alcohol consumption. It is of interest that serum SA seems to be a sensitive indicator for alcohol drinking especially in women since the markers used today, in particular CDT, have poorer clinical utility in women than in men. This evaluation of a new potential marker for alcohol abuse suggests that SA may have diagnostic value, alone or in combination with other markers, for screening, to follow treatment and to detect relapse.

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