N-acetyltransferase 2 polymorphism is not related to the risk of advanced alcoholic liver disease.
BACKGROUND
Ethanol abuse is the most prevalent cause of liver cirrhosis in Spain. Genetic polymorphisms affect the activity of the enzymes involved in ethanol metabolism and in processing the toxic by-products generated in the liver. N-acetyltransferase 2 (NAT2) is a polymorphic phase 2 enzyme not involved in these processes, but recent data suggest that the most prevalent slow acetylator genotype protects against the risk of advanced alcoholic liver disease (ALD). We have identified six single nucleotide polymorphisms (SNP) at the NAT2 gene locus in order to disclose whether such an association exists.


METHODS
Genomic DNA from 95 ALD patients (15 with superimposed hepatocellular carcinoma (HCC)) and from 258 healthy individuals was analysed for SNPs at the coding region of the NAT2 gene by means of allele-specific polymerase chain reaction.


RESULTS
There are no differences in the relative frequencies of the eight identified NAT2 alleles (including the wild-type allele) nor in the distribution of predicted phenotypes (54% of slow acetylators in each group). Twelve patients with HCC (80%) were slow acetylators (P < 0.05).


CONCLUSIONS
There is no relationship between the NAT2 genotype and the risk of ALD. Slow acetylator genotype may predispose to the development of HCC in severe ALD patients not infected by the hepatitis C virus.
Agúndez
J A G
JA
Dept of Pharmacology, School of Medicine, University of Extremadura, Badajoz, Spain.
Ladero
J M
JM
Olivera
M
M
Lozano
L
L
Fernández-Arquero
M
M
de laConcha
E G
EG
Díaz-Rubio
M
M
Benitez
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human