Prevalence of C282Y, H63D, and S65C mutations in hereditary HFE-hemochromatosis gene in Lithuanian population

Abstract

HFE-hemochromatosis is a common autosomal recessive disease caused by HFE gene mutations and characterized as iron overload and failure of different organs. The aim of this study was to determine the prevalence of C282Y (c.845 G>A), H63D (c.187 C>G), and S65C (c.193A>T) alleles of HFE gene in the Lithuanian population. One thousand and eleven healthy blood donors of Lithuanian nationality were examined in four different ethnic Lithuanian regions to determine HFE gene alleles and genotype frequencies. The samples of DNA were analyzed for the presence of restriction fragment length polymorphism and validated by DNA sequencing. Among 1,011 blood donors tested, the frequency of C282Y, H63D, and S65C alleles were 2.6%, 15.9%, and 1.9%, respectively. One third of the tested subjects (n = 336) had at least one of the C282Y or H63D HFE gene mutations. The screening of Lithuanian blood donors has detected 13 (1.3%) subjects with a genotype C282Y/C282Y or C282Y/H63D responsible for the development of HFE-hemochromatosis. The prevalence of C282Y mutation was significantly higher among the inhabitants of Zemaitija (Somogitia) at the Baltic Sea area (5.9%) in comparison to the regions of continental part of Lithuania (2.4% in Dzukija, 2.3% in Aukstaitija, and 2% in Suvalkija, p < 0.05). These data support the hypothesis that the p.C282Y mutation originated from Scandinavia and spread with the Vikings along the Baltic Sea coast. The first epidemiological investigation of HFE gene mutations in ethnic Lithuanians showed that the frequencies of H63D, C282Y, and S65C of HFE gene alleles are similar to the other North-Eastern Europeans, especially in the Baltic region (Estonia, Latvia), Poland, and part of Russia (Moscow region).

The H63D Mutation of the Hemochromatosis Gene is Associated with Sustained Virological Response in Chronic Hepatitis C Patients Treated with Interferon-Based Therapy: A Meta-Analysis

“…Finally, it was recently reported that patients infected with HCV genotype 3a had higher expression of hepatic MHC class I and HFE (Cardoso et al 2004). Considering that the C282Y mutation is reported more rarely than the H63D mutation (Candore et al 2002;Kucinskas et al 2012), it is not surprising that the number of C282Y-carrying patients was small in the studies in our meta-analysis. Meanwhile, in three of the enrolled studies, patients with the C282Y mutation displayed no SVR; however, the group of C282Y patients was too small to allow for detection of a statistically significant difference from the WT group (i.e.…”

“…Subsequent stratification analysis revealed that the highest frequencies of C282Y occurred in the Irish (10.0%) and of H63D in the Basque (30.4%) . In contrast, the frequency of S65C mutation was lower than that of C282Y or H63D in all regions examined (Candore et al 2002;Kucinskas et al 2012).…”

“…Three mutations have been identified in the HFE gene. One mutation produces an amino acid substitution of cysteine for tyrosine at position 282 (C282Y, nucleotide 845G>A), the second mutation replaces histidine with aspartic acid at position 63 (H63D, 187C>G), and the third mutation replaces serine with cysteine at position 65 (S65C, 187A>T) Arya et al 1999;Merryweather-Clarke et al 2000;Kucinskas et al 2012). The prevalence of HFE mutations varies greatly among populations from different geographical regions.…”

Association between inherited monogenic liver disorders and chronic hepatitis C

“…Hereditary hemochromatosis is characterized by excessive iron overload and is most commonly caused by HFE gene mutations [2] . The frequency of the most common HFE mutation, C282Y, is 0.035 in Latvia and 0.026 Lithuania; however, the frequency of hereditary hemochromatosis is lower at 0.013 [5] . Alpha-1 antitrypsin deficiency is caused by the absence of the proteinase inhibitor alpha-1 antitrypsin, and affected patients develop liver disease and emphysema in the third or fourth decade of life [3] .…”

PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population

“…The patients in liver fibrosis group underwent percutaneous liver biopsy and were included in the study if stage 1 to 3 fibrosis was documented by histological evaluation using METAVIR score [15]. Control samples came from our previous genotyping study on the prevalence of HFE mutations in the Lithuanian population and included 498 voluntary, unrelated Lithuanian blood donors [16]. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki (6th revision, 2008).…”