INFLUENCE OF GENETIC-VARIATION IN ALCOHOL AND ALDEHYDE DEHYDROGENASE ON SEROTONIN METABOLISM

The influence of genetic variation in alcohol dehydrogenase (ADH; EC 1 .1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) on the metabolic pattern of serotonin (5-hydroxytryptamine, 5-HT) in humans was examin ed from the relative urinary concentrations of the end products 5-hydr oxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL). Hea lthy Caucasian (Swedish) and Oriental (Chinese) subjects were genotype d for ADH2, ADH3 and ALDH2 by a PCR/SSCP technique. The 5-HTOL/5-HIAA ratios ranged between 0.9-9.4 pmol/nmol (4.4 +/- 1.8, mean +/- SD, n = 143). No significant difference in the 5-HT metabolic pattern was obs erved between Caucasians and Orientals (4.3 +/- 1.8 and 4.4 +/- 1.8 pm ol/nmol, respectively), nor between any of the ADH2, ADH3 and ALDH2 ge notypes. Despite the modulatory effects of genetic variation of these enzymes on ethanol metabolism, the present results indicate that the i ndividual isozyme composition of ADH2, ADH3 and ALDH2 is not important for the metabolic pattern of 5-HT.