Genetic polymorphism of the rat aldehyde dehydrogenase 2 and the severity of experimental alcohol-induced liver damage

Abstract

In humans, alcoholic liver disease in the heterozygotes of the aldehyde dehydrogenase (ALDH) 2 gene is more severe than that in the normal homozygotes. Recently, a substitution (G for A) was identified in the cDNA of alcohol-nonpreferring (NP) rats which changes amino acid 67 from Gln (CAG codon; ALDH2^Q allele) to Arg (CGG codon; ALDH2^R allele). To determine whether the ALDH2 polymorphism was associated with the development of alcoholic liver damage in the each 15 alcohol-fed and control rats, we genotyped the ALDH2 locus by polymerase chain reaction (PCR) amplification followed by electrophoresis after digestion with DdeI. The frequencies of ALDH2 genotype in commercially available Sprague-Dawley rats were 36.7% for the $\text{ALDH2}{}^{\mathrm{<mtext>Q</mtext>}}\text{ALDH2}{}^{\mathrm{<mtext>Q</mtext>}}$, 53.3% for the $\text{ALDH2}{}^{\mathrm{<mtext>Q</mtext>}}\text{ALDH2}{}^{\mathrm{<mtext>R</mtext>}}$ and 10.0% for the $\text{ALDH2R}\text{ALDH2R}$, respectively. Hepatic collagen-bound hydroxyproline was higher in the ethanol-fed rats with $\text{ALDH2}{}^{\mathrm{<mtext>Q</mtext>}}\text{ALDH2}{}^{\mathrm{<mtext>R</mtext>}}$ or $\text{ALDH2}{}^{\mathrm{<mtext>R</mtext>}}\text{ALDH2}{}^{\mathrm{<mtext>R</mtext>}}$ than in the ethanol-fed rats with $\text{ALDH2}{}^{\mathrm{<mtext>Q</mtext>}}\text{ALDH2}{}^{\mathrm{<mtext>R</mtext>}}$. The ALDH2^R allele may be associated with the severity of experimental alcohol-induced liver damage.