Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis.
Hepatology
; 36(6): 1355-60, 2002 Dec.
Article
en En
| MEDLINE
| ID: mdl-12447859
ABSTRACT
The role of genetic factors in the pathogenesis of alcohol-induced liver disease (ALD) is receiving increasing attention. Recently, it has been reported that homozygosity for a valine to alanine substitution in the mitochondrial targeting sequence of manganese superoxide dismutase (Mn-SOD) represents a risk factor for severe ALD. Because this mutation is postulated to modify enzyme transport into mitochondria, we have sought confirmatory evidence of this association in a larger group of patients and investigated whether this polymorphism might influence alcohol-induced oxidative stress. Genotyping for the valine-alanine (Val-Ala) polymorphism of the Mn-SOD gene in 281 patients with advanced ALD (cirrhosis/fibrosis) and 218 drinkers without liver disease showed no differences in either the heterozygote (55% vs. 50%) or the homozygote (19% vs. 23%) frequency for the alanine allele. By measuring the titers of circulating antibodies against oxidized cardiolipin (OX-CL) and malondialdehyde (MDA) or hydroxy-ethyl radical (HER) adducts as markers of oxidative stress, we found a significant increase in ALD patients compared with healthy controls. However, the carriers of the alanine Mn-SOD allele had titers of anti-MDA, anti-HER, and anti-OX-CL IgG comparable with heterozygotes and patients homozygous for the valine allele. Similarly, the frequency of subjects with antibody titers above the 95th percentile of controls was not increased among homozygotes for the alanine Mn-SOD allele. In conclusion, in our population Val-Ala polymorphism in Mn-SOD influences neither susceptibility to alcohol-induced liver fibrosis nor alcohol-induced oxidative stress.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Superóxido Dismutasa
/
Polimorfismo de Nucleótido Simple
/
Hepatitis Alcohólica
/
Cirrosis Hepática
Tipo de estudio:
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Hepatology
Año:
2002
Tipo del documento:
Article
País de afiliación:
Reino Unido