Association of HFE gene C282Y and H63D mutations with liver cirrhosis in the Lithuanian population.
OBJECTIVE
Liver cirrhosis is the end-stage disease of chronic liver injury. Due to differences in the natural course of chronic liver diseases, identification of genetic factors that influence individual outcomes is warranted. HFE-linked hereditary hemochromatosis (HH) predisposes disease progression to cirrhosis; however, the role of heterozygous C282Y or H63D mutations in the development of cirrhosis in the presence of other etiological factors is still debated. The aim of this study was to determine the association between heterozygous C282Y and H63D mutations and non-HH liver cirrhosis in Lithuanian population.


METHODS
The patient cohort consisted of 209 individuals. Diagnosis of cirrhosis was confirmed by clinical, laboratory parameters, liver biopsy, and radiological imaging. Control samples were obtained from 1005 randomly selected unrelated healthy individuals. HFE gene mutations were determined using the PCR-RFLP method.


RESULTS
The most common causes of cirrhosis were hepatitis C (33.9%), hepatitis B (13.6%), and alcohol (25.8%). C282Y allele was associated with the presence of cirrhosis (OR=2.07; P=0.005); this was also observed under recessive model for C282Y (OR=2.06, P=0.008). The prevalence of C282Y allele was higher in cirrhotic men than in controls (7.0% vs. 2.8%, P=0.002). The carriage of H63D risk allele (OR=1.54; P=0.02), heterozygous C282Y/wt and homozygous H63D/H63D genotypes were associated with liver cirrhosis in males (OR=2.48, P=0.008, and OR=4.13, P=0.005, respectively).


CONCLUSIONS
Heterozygous C282Y mutation of the HFE gene was associated with liver cirrhosis in the Lithuanian population. In gender-related analysis, heterozygous C282Y and homozygous H63D mutations were linked to liver cirrhosis in men, not in women.
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Simonas
S
Juzėnas
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania; Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Juozas
J
Kupčinskas
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania; Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Irena
I
Valantienė
Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jolanta
J
Šumskienė
Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Vitalija
V
Petrenkienė
Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jūrate
J
Kondrackienė
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Laimutis
L
Kučinskas
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania; Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania. Electronic address: gediminaskiudelis@gmail.com.
Gediminas
G
Kiudelis
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jurgita
J
Skiecevičienė
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania; Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Limas
L
Kupčinskas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008097:Lithuania / Q000453:epidemiology; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012189:Retrospective Studies; D012737:Sex Factors
C103673:HFE protein, human; D000071020:Hemochromatosis Protein
C282Y; H63D; HFE; Liver cirrhosis