Affiliations: University of Debrecen, Medical and Health Science
Center, Faculty of Public Health, Department of Preventive Medicine, Debrecen,
Hungary | Public Health Research Group of the Hungarian Academy
of Sciences, Faculty of Public Health, Medical and Health Science Centre,
University of Debrecen, Debrecen, Hungary | London School of Hygiene and Tropical Medicine,
London, UK
Note: [] Corresponding author: Roza Adany MD, Ph.D., D.Sc. University of
Debrecen, Medical and Health Science Center, Faculty of Public Health,
Department of Preventive Medicine, Kassai str. 26/b, Debrecen, Hungary. Tel.:
+36 52 417 267; Fax: +36 52 417 267; E-mail: adany.roza@sph.unideb.hu
Abstract: The aim of this study was to analyze the combined effect of the most
frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B,
Arg272Gln and Ile350Val in ADH1C) on the alcohol use habits, alcohol dependence
and chronic liver diseases in Hungary. The study included men, aged 45–64 years. Altogether, 241
cases with chronic liver disease (CLD) and 666 randomly selected controls
without CLD were analysed for all four polymorphisms. Associations between the
polymorphisms, individually, and in combination, and excessive and problem
drinking and CLD, were assessed using logistic regression. In this study we have identified a novel mutation, called ADH1B
Arg370His. The ADH1C Arg272Gln and Ile350Val showed almost complete linkage.
The 272Gln/35Val allele increased the risk of excessive and problem drinking in
homozygous form (OR=1.582, p=0.035, CI=1.034–2.421, OR=1.780, p=0.016,
CI=1.113–2.848, respectively). The joint analysis showed that when
combined with the wild type ADH1C Arg272/Ile350 allele, the ADH1B 48His is
protective against CLD (OR=0.368, p=0.019, CI=0.159–0.851). The results obtained in the study help not only to clarify the
effects of different ADH SNPs but to better understand how these polymorphisms
modify each other's effects in the development of alcoholism and related
diseases.
