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Alcohol and Alcoholism Advance Access originally published online on April 20, 2006
Alcohol and Alcoholism 2006 41(4):364-367; doi:10.1093/alcalc/agl024
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© The Author 2006. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved

DIFFERENT ALLELE-DISTRIBUTION OF MTHFR 677 C -> T AND MTHFR –393 C -> A IN PATIENTS CLASSIFIED ACCORDING TO SUBTYPES OF LESCH'S TYPOLOGY

DOMINIKUS BÖNSCH*, KRISTINA BAYERLEIN, UDO REULBACH, ROLAND FISZER, THOMAS HILLEMACHER, WOLFGANG SPERLING, JOHANNES KORNHUBER and STEFAN BLEICH

Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany

* Author to whom correspondence should be addressed at: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6 91054 Erlangen, Germany. Tel.: +49 9131 8536362; Fax: +49 9131 8534105; E-mail: dominikus.boensch{at}psych.imed.uni-erlangen.de

(Received 3 November 2005; first review notified 15 December 2005; in revised form 13 Feburary 2006; accepted 27 Feburary 2006)

Aims: The typology by Lesch distinguishes between four subtypes: type 1 (model of allergy), type 2 (model of anxiety or conflict), type 3 (alcohol as an antidepressant), and type 4 (alcohol as adaptation). Taking into account that alcohol dependence is associated with elevated homocysteine levels, this study was undertaken to investigate different MTHFR (methylenetetrahydrofolate reductase) genotypes related to homocysteine metabolism in patients with alcohol dependence who were classified according to Lesch's typology (LT). Subjects and methods: 134 non-abstinent chronic alcoholics (112 males, 22 females; mean age 44.2 (SD 8.9) years) were classified according to LT and divided into four groups: LT 1 (n = 26), LT 2 (n = 65), LT 3 (n = 58), and LT 4 (n = 18). Total plasma homocysteine levels and MTHFR genotypes –393, 677, and 1793 were determined. Results: We observed a significantly higher frequency of the thermolabile MTHFR 677 C->T variant (TT) in patients classified as subtype LT4 when compared with subtypes LT2 and LT3 (P = 0.005). Furthermore, for the MTHFR –393 C -> A-polymorphism, significantly more AC/AA variants were found in subtype LT4 (P = 0.034). No differences in allele-distribution were detected for MTHFR 1793. Conclusion: To our knowledge, this is the first study evaluating MTHFR genotypes in patients who were classified according to LT. Significantly different distributions of MTHFR 677 and –393 variants within Lesch Type 4 as compared with Types 2 and 3 hint at genetic determination of Lesch subtypes.


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