Association of the epsilon 2 allele of APOE gene to hypertriglyceridemia and to early-onset alcoholic cirrhosis.
BACKGROUND
The diverse incidence of alcoholic cirrhosis around the world and the fact that not all alcoholic drinkers develop liver disease indicates that genetic and environmental factors play an important role in the development of liver cirrhosis. Lipids participate in early stages of alcoholic cirrhosis. Therefore variations in the plasma lipid profile due to primary (genetic) or secondary (environmental) dyslipidemia could affect the development of liver disease. The aim of this study was to analyze the lipid profile and apolipoprotein E (APOE) polymorphism in patients with alcoholic liver cirrhosis (AC) and determine the risk associated with genotype polymorphism with the onset of alcoholic cirrhosis.


METHODS
In a case and control study, 86 patients with AC divided into hyperlipidemic (H) and non-hyperlipidemic (non-H) groups, and 133 healthy individuals (C) matched by age and sex were studied. Lipid profile and liver function tests were measured by enzymatic methods. The APOE genotypes were identified by PCR-RFLP's.


RESULTS
A statistically significant increase of the APOE*2 allele and genotypes 2/2, 2/3, and 2/4 was present in AC patients compared to C group. A hyperlipidemic state characterized by increased levels of triglycerides and apolipoprotein B (APOB) and a decrease of high density lipoprotein-cholesterol (HDL-c) was detected in young-aged patients (31.2 +/- 6.2 years old vs. 46.3 +/- 12.5 years old). In this group, hypertriglyceridemia was closely associated to APOE*2 allele and to an early onset of liver cirrhosis. By contrast, APOE*4 allele was associated with a longer duration of alcohol intake (>20 years) in the non-H group.


CONCLUSIONS
This study shows the association of hypertriglyceridemia and APOE allele with the early onset of alcoholic liver cirrhosis, and the interaction between environmental factors, such as duration of alcohol abuse and amount of alcohol intake, and genetic factors (APOE*2 allele) on the hypertriglyceridemic process.
Hernández-Nazará
Zamira H
ZH
Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México.
Ruiz-Madrigal
Bertha
B
Martínez-López
Erika
E
Roman
Sonia
S
Panduro
Arturo
A
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D053329:Apolipoprotein E2 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics
D053329:Apolipoprotein E2