Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan

Mah, Yone-Han; Kao, Jia‐Horng; Liu, Chun‐Jen; Chen, Chi‐Ling; Chen, Pei‐Jer; Lai, Ming‐Yang; Chen, Ding‐Shinn

doi:10.1111/j.1478-3231.2005.01055.x

Cited by 20 publications

(14 citation statements)

References 40 publications

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“…Our data showed that the GNPAT variant plays a role in iron phenotype (increased serum iron levels at fasting and after supplementation) in healthy young Taiwanese women, a population that does not carry the HFE C282Y mutation. (5) Our findings suggest that GNPAT p.D519G is not an "HFE modifier," as proposed by McLaren et al, but is an independent player in hepcidin regulation. Further in vitro and human studies will be required to clarify the exact role of GNPAT in iron phenotype.…”

Section: To the Editorsupporting

confidence: 55%

GNPAT variant is associated with iron phenotype in healthy Taiwanese women: A population without the HFE C282Y mutation

2016

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McLaren et al.(1) recently used whole-exome sequencing to show that GNPAT p.D519G (rs11558492) is associated with a high-iron phenotype in HFE C282Y homozygous men. Three other studies examined this association in different Caucasian populations with conflicting results. (2)(3)(4) However, the role of GNPAT in the absence of iron overload or in the HFE wild-type population remains unclear.Here, we investigated iron indices before and after iron supplementation and their association with genetic polymorphisms. This study was approved by the ethics committee, and informed consent was obtained from all participants. We screened healthy reproductive-age women and excluded those with renal insufficiency, anemia, gastrointestinal bleeding, or chronic inflammation and those that were pregnant or breastfeeding; thus, 83 healthy female volunteers were eligible for analysis. Participants fasted overnight, and baseline iron parameters were measured at 8 AM. They were then administered sodium ferrous citrate (element iron, 100 mg), and blood was sampled 2 hours later. Data are presented in Table 1.Regarding TMPRSS6 rs855791, iron parameters at baseline or after iron challenge did not significantly differ between genotypes. For GNPAT rs11558492, 64 participants were wild type (A/A) and 19 carried variants (18 A/G and 1 G/G). The G allele frequency was 12% (20 of 166), similar to 14% in the general population in 1000 Genomes (chi-square test: P 5 0.416). Fasting serum iron levels were higher in subjects with GNPAT variants than in wild-type subjects (131.2 vs. 110.5 lg/dL; P 5 0.045), but there was no significant difference in fasting transferrin saturation (TS; 38.2% vs. 33.7%; P 5 0.153). After iron supplementation, serum iron levels and TS were both significantly higher in GNPAT variants (iron, 320.2 vs. 284.5 lg/dL; P 5 0.025; TS, 85.8% vs. 78.9%; P 5 0.040). Furthermore, multivariate analysis showed that the GNPAT genotype was an independent factor associated with baseline iron levels (P 5 0.045; adjusted R 2 5 0.037); the factors analyzed included age,

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Section: To the Editorsupporting

confidence: 55%

GNPAT variant is associated with iron phenotype in healthy Taiwanese women: A population without the HFE C282Y mutation

2016

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“…In addition, the homozygous C282Y status was absent from individuals with chronic hepatitis as well as controls. Overall, these findings are in agreement with well documented studies from the Middle-East and eastern-Asia [Mah et al, 2005;Ghaziani et al, 2007] but differ from the report of Sendi et al [2005] showing that in Iranians patients, the frequency of major mutation C282Y in HFE gene with HBV infection is higher than control subjects (4% vs. 0%, P ¼ 0.02). However, it must be stressed that the latter study was performed on a limited number of patients (n ¼ 75).…”

Section: Discussionsupporting

confidence: 83%

“…In Morocco, available data were limited regarding HFE gene mutations [Ezzikouri et al, 2008]. In addition, only few studies have focused on the relationship between HFE mutations and the persistence of HBV infection [Mah et al, 2005;Sendi et al, 2005;Ghaziani et al, 2007]. The aim of the current study was to determine whether there is any difference between the frequencies of HFE mutations in patients with HBsAg and patients infected with hepatitis C virus (HCV), compared with an appropriate control group.…”

Section: Introductionmentioning

confidence: 95%

Influence of mutation of the HFE gene on the progression of chronic viral hepatitis B and C in Moroccan patients

Ezzikouri

Rebbani

Ababou

et al. 2011

Journal of Medical Virology

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The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. The aim of the present study was to measure the frequencies of the common HFE gene mutations in Moroccan subjects with chronic viral hepatitis B and C and to assess their influence on the progression of liver disease. H63D and C282Y mutations were screened by the polymerase chain reaction followed by restriction fragment length polymorphism analysis in 170 chronic hepatitis B patients, 168 chronic hepatitis C patients, and 200 healthy controls. A very small proportion of patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV; 1.8% and none, respectively) were heterozygous for the C282Y mutation, that is, rates not statistically different from those observed in healthy control (2%, P > 0.05). Similarly, the frequency of the H63D allele was not significantly different between HBV (13.8%) or HCV (14.3%) patients and controls (13.5%, P > 0.05). Multivariate analysis showed that carriers of the H63D mutation infected with HBV are at higher risk to progress towards an advanced liver disease when compared with patients infected with HBV with wild-type (OR = 2.45, 95% CI = 1.07-5.58). In contrast, no association between HFE mutated HCV-infected patients and an increased risk of disease progression was found (OR = 1.24, 95% CI = 0.61-2.50, P = 0.547). In conclusion, in Morocco the frequency of the HFE C282Y allele is very low and H63D mutation carriage occurs in almost 14% of the patients, a rate similar in chronic hepatitis patients and healthy controls. In the case of chronic hepatitis B, the carriage of the H63D variant represents a risk factor of evolution towards a more active disease.

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“…It may therefore be of interest to study whether patients with chronic hepatitis B or chronic heavy alcohol consumption who harbour the H63D mutaion are at greater risk of progression to cirrhosis than their counterparts who do not have this mutated allele. Few authors did not however find this relationship in their studies [21][22][23][24].…”

Section: Discussionmentioning

confidence: 77%

“…It is possible that mutation in this gene predisposes to development of cirrhosis in the presence of another cause of chronic inflammation of the liver such as chronic hepatitis B infection or alcohol. Several earlier studies have shown that H63D heterozygosity is associated with an increased risk for liver fibrosis and cirrhosis [19,21,22]. It may therefore be of interest to study whether patients with chronic hepatitis B or chronic heavy alcohol consumption who harbour the H63D mutaion are at greater risk of progression to cirrhosis than their counterparts who do not have this mutated allele.…”

Section: Discussionmentioning

confidence: 98%

Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population

Jain

Agarwal

Tamhankar

et al. 2011

Indian J Gastroenterol

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Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan

Cited by 20 publications

References 40 publications

GNPAT variant is associated with iron phenotype in healthy Taiwanese women: A population without the HFE C282Y mutation

GNPAT variant is associated with iron phenotype in healthy Taiwanese women: A population without the HFE C282Y mutation

Influence of mutation of the HFE gene on the progression of chronic viral hepatitis B and C in Moroccan patients

Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population

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