PÁCAL, Lukáš, Petr HUSA, Vladimír ZNOJIL and Kateřina KAŇKOVÁ. HFE C282Y gene variant is a risk factor for the progression to decompensated liver disease in chronic viral hepatitis C subjects in Czech population. Hepatology Research. England: Blackwell Publishing, 2007, vol. 37, No 9, p. 740-7, 8 pp. ISSN 1386-6346.
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Basic information
Original name HFE C282Y gene variant is a risk factor for the progression to decompensated liver disease in chronic viral hepatitis C subjects in Czech population
Name in Czech Varianta HFE C282Y je rizikovým faktorem dekompenzace chronické virové hepatitidy C v české populaci
Authors PÁCAL, Lukáš (203 Czech Republic, guarantor), Petr HUSA (203 Czech Republic), Vladimír ZNOJIL (203 Czech Republic) and Kateřina KAŇKOVÁ (203 Czech Republic).
Edition Hepatology Research, England, Blackwell Publishing, 2007, 1386-6346.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30202 Endocrinology and metabolism
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 1.892
RIV identification code RIV/00216224:14110/07:00021963
Organization unit Faculty of Medicine
UT WoS 000247806000009
Keywords in English hepatitis; HFE; iron; polymorphism
Tags hepatitis, HFE, Iron, polymorphism
Tags International impact, Reviewed
Changed by Changed by: Mgr. Lukáš Pácal, Ph.D., učo 14473. Changed: 24/6/2009 10:06.
Abstract
Aims: To determine the prevalence of selected HFE polymorphisms (C282Y, H63D and S65C) among patients with chronic viral hepatitis B and C and to investigate their role in the progression of liver disease. Subjects and methods: A total of 207 subjects with chronic B or C viral hepatitis and 243 healthy controls were enrolled in the case control study. Cases were further classified according to the clinical stage of liver disease into three groups: (A) virus carriers, (B) compensated resp. (C) decompensated liver disease. HFE polymorphisms were detected by PCR-based methodology. Fisher exact, chi-square and Kruskal-Wallis tests were used to test for differences in variables studied between groups. Haplotypes were inferred in silico and their distribution compared by permutation test. Modified survival (time-to-event) analysis was used to test for the differences in the progression to the decompensated liver disease in carriers of C282Y wild-type vs. mutated genotypes. Results: The frequency of HFE genotypes, alleles and haplotypes differed neither between HBV nor HCV patients vs. controls. In HCV subjects (i) the frequency of the 282Y allele was significantly higher in the (C) group compared to (B) group (12.5 vs. 2.2%, respectively, P=0.002, Fisher exact test), and (ii) carriers of the 282Y mutation exhibited significantly faster progression to decompensated liver disease than wild-type carriers (P=0.044, log-rank test). Conclusion: Carriage of the minor of the HFE C282Y polymorphism is associated with decompensated liver disease and its earlier onset in the subjects with chronic viral hepatitis C in Czech population.
Abstract (in Czech)
Cílem práce bylo zjistit prevalenci HFE polymorfizmů (C282Y, H63D a S65C) u pacientů s chronickou virovou hepatitidou B a C a zkoumat jejich vliv na rozvoj jaterního poškození. Do studie bylo zařazeno celkem 207 osob s chronickou virovou hepatitidou B/C a 243 kontrol. Pacienti byli dále rozděleni podle klinického stavu na: (A) vironosiče, (B) kompenzované a (C) dekompenzované. DNA byla izolována z leukocytů periferní krve a polymorfizmy v HFE genu byly detekovány pomocí PCR. Fisher exact, chí-kvadrát a Kruskal-Wallisův test byly použity ke srovnání parametrů mezi skupinami. Haplotypy byly rekonstruovány pomocí software PHASE. Nezjistili jsme významný rozdíl v alelických ani genotypových frekvencích žádné z variant mezi pacienty B vs. C vs. kontrolami. K testování rozdílů v progresi choroby mezi pacienty s wild-type genotypem a nosiči mutace byla použita analýza přežívání. U osob s hepatitidou C byla frekvence alely 282Y signifikantně vyšší ve skupině (C) ve srovnání se skupinou (B) (12.5 vs. 2.2%, P=0.002, Fisher exact test) a u nosičů polymorfizmu 282Y byla zjištěna rychlejší progrese choroby než u osob s wild-type genotypem (P=0.044, log-rank test). Závěr: Nosičství minoritní alely polymorfizmu HFE C282Y je spojeno s rychlejším nástupem dekompenzace jaterní choroby u pacientů s chronickou virovou hepatitidou C v české populaci.
Links
MSM 141100002, plan (intention)Name: Molekulární patofyziologie multigenních chorob
Investor: Ministry of Education, Youth and Sports of the CR, Molecular pathophysiology of multigene diseases
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