HFE H63D

Occupational exposure to lead (Pb) continues to be a serious public health concern and may pose an elevated risk of genetic oxidative damage. In Brazil, car battery manufacturing and recycling factories represent a great source of Pb contamination, and there are no guidelines on how to properly protect workers from exposure or to dispose the process wastes. Previous studies have shown that Pb body burden is associated with genetic polymorphisms, which consequently may influence the toxicity of the metal. The aim of this study was to assess the impact of Pb exposure on DNA oxidative damage, as well as the modulation of hemochromatosis (HFE) polymorphisms on Pb body burden, and the toxicity of Pb, through the analysis of 8-hydroxy-2'-deoxyguanosine (8-OHdG), in subjects occupationally exposed to the metal...

Hemochromatosis is a genetic disorder marked by abnormally high levels of intestinal iron absorption leading to severe end-organ damage. It is classically associated with HFE gene mutations, including C282Y and H63D, but in recent years, many non-HFE mutations along with novel variants have been discovered, particularly among non-Whites. We describe a case of an elderly Japanese patient who was evaluated for markedly elevated ferritin found to have hemochromatosis, with no hepatic fibrosis while being negative for HFE and common non-HFE gene mutations...

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, along with steatosis and non-alcoholic steatohepatitis (NASH), and is associated with cirrhosis and hepatocellular carcinoma. Candidate gene and genome-wide association studies have validated the relationships between NAFLD, NASH, PNPLA3 , TM6SF2 , and HFE . The present study utilized five polymorphisms in three genes: PNPLA3 (I148M and K434E) TM6SF2 (E167K), and HFE (H63D and C282Y), based on undocumented case-control studies in the Saudi Arabian population...

Background: Hereditary hemochromatosis (HH) occurs due to mutations in the HFE gene. While the C282Y mutation is the most common genotype reported in HH, other genotypes are found less frequently, indicating variable degrees of penetrance. We studied the penetrance of the C282Y/H63D compound heterozygote genotype in developing clinically significant iron overload. Methods: We have completed a retrospective analysis on every individual within Newfoundland & Labrador who were diagnosed as C282Y/H63D compound heterozygote between 1996 and 2009 through a molecular genetics study...

BACKGROUND: Wilson's disease (WD) is a rare inherited disorder of copper metabolism. Treatment consists of chelating agents, but side effects are common. We describe a patient who developed colitis during trientine treatment leading to decompensation of liver cirrhosis. CASE SUMMARY: A healthy 51-year-old woman was diagnosed with liver cirrhosis due to decompensation with ascites. Etiologic evaluation raised suspicion of hereditary hemochromatosis because of compound heterozygosity HFE p...

The short oligodeoxynucleotide (ODN) probes are suitable for good discrimination of point mutations. However, the probes suffer from low melting temperatures. In this work, the strategy of using acridine-4-carboxamide intercalators to improve thermal stabilisation is investigated. The study of large series of acridines revealed that optimal stabilisation is achieved upon decoration of acridine by secondary carboxamide carrying sterically not demanding basic function bound through a two-carbon linker. Two highly active intercalators were attached to short probes (13 or 18 bases; designed as a part of HFE gene) by click chemistry into positions 7 and/or 13 and proved to increase the melting temperate (Tm) of the duplex by almost 8°C for the best combination...

BACKGROUND: Little is known about the prevalence of HFE (homeostatic iron regulator) hemochromatosis in African Americans (AA). METHODS: We defined AA as self-identified AA, blacks, or non-Hispanic blacks. We defined hemochromatosis-associated HFE genotypes as p.C282Y/p.C282Y and p.C282Y/p.H63D. We compiled prevalences of these genotypes in AA using published population and cohort data and numbers of men and women ≥18 y‬ in 2018 U.S. Census estimates...

Autoimmune hepatitis (AIH) is an inflammatory condition of the liver that is characterized by high titers of certain autoantibodies in the serum. As in other chronic inflammatory conditions, the transferrin saturation in patients with AIH is typically low. However, in rare instances, AIH has been reported to be associated with elevated transferrin saturation secondary to heterozygous HFE gene ( H63D ) mutation. This report describes one such case in which the patient had characteristic histopathologic findings of AIH but was also found to have iron overload and heterozygous H63D mutation on genetic testing, leading to the initial dual differential diagnosis of AIH and hemochromatosis, which highlighted the further need of obtaining a liver biopsy...

Introduction: Co-inheritance of hereditary hemochromatosis ( HFE ) gene variants p . C282Y and p .H63D worsen iron overload in transfusion-dependent thalassemia. Data on the HFE gene variants in Sri Lankan patients with thalassemia have not been extensively studied. This study aimed to analyze the p .C282Y and p .H63D variants in transfusion-dependent beta (β) and HbE/β-thalassemia patients and establish an association between these variants and their serum ferritin levels. Materials and Methods: A total of 125 transfusion-dependent β-thalassemia major and HbE/β thalassemia patients were tested for the c...

BACKGROUND: Screening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized. METHODS: We studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a) elevated serum ferritin (SF) and transferrin saturation (TS) at screening and CE, and b) absence of IO treatment, anemia, transfusion >10 units, alcohol intake >30 g/d, hepatitis B or C, and pregnancy...

In a newborn with very precocious liver failure, cholestatic jaundice, and low γ-glutamyl transpeptidase, progressive hepatosplenomegaly induced a progressively worsening respiratory distress, that was successfully treated with steroids. Laboratory and genetic tests did not find any disease usually associated with neonatal cholestasis. However, the patient was positive for a homozygous mutation of the HFE gene, which is associated with hereditary hemochromatosis, a disease with typical onset in adulthood. Although no firm conclusions can be drawn from a single clinical case, this experience suggests that hereditary hemochromatosis could have played a role in the induction of this serious cholestasis, probably already arisen in the uterus...

In clinical trials, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) use alone in persons with type 2 diabetes (T2D) or testosterone replacement therapy (TRT) prescription alone in men with hypogonadism was shown to lead to a modest but significant increase in red blood cell mass. Recent evidence indicates that combined use of TRT and SGLT-2i in persons with T2D may be associated with risk of erythrocytosis. However, factor(s) that may lead to the development of erythrocytosis in these patients is unknown...

BACKGROUND AND AIMS: Hereditary hemochromatosis (HH) is associated with increased risk of hepatocellular carcinoma (HCC). However, HCC risk factors within this population and across various HFE genotypes remain unclear. METHODS: We conducted a retrospective cohort study of patients with ≥ 1 HFE genotype test in the Veterans Health Administration. We followed patients until HCC, death, or 6/30/19. We calculated incidence rates (IRs) and used Cox proportional hazards models to estimate HCC risk...

We analysed iron biomarkers and their relationships in 30 subjects with HFE mutations and moderate hyperferritinaemia undergoing iron removal at our blood donation centre. Body mass index (BMI) and liver enzymes were assessed. Serum iron (SI), ferritin, transferrin saturation (TSAT), hepcidin and non-transferrin bound iron (NTBI) were measured serially. Seventeen subjects had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median age (p = 0.582), BMI (p = 0.500) and ferritin (p = 0.089) were comparable...

BACKGROUND: In European ancestry populations, iron overload disorder Hereditary Hemochromatosis (HH) is predominantly caused by HFE p.C282Y and p.H63D mutations. Male p.C282Y homozygotes have markedly increased hepatic malignancy incidence but risks for other cancers in male and female homozygotes are unclear. METHODS: 451,143 UK Biobank European ancestry participants (aged 40-70 years; 54.3% female) were followed (mean 11.6 years) via hospital admissions and national cancer registries...

Iron overload disorders represent a variety of conditions that lead to increased total body iron stores and resultant end-organ damage. An elevated ferritin and transferrin-iron saturation can be commonly encountered in the evaluation of elevated liver enzymes. Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D, mutations most encountered in hereditary hemochromatosis, should be pursued in evaluation of hyperferritinemia. Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy (especially if liver disease is a cause of iron overload) should be used as appropriate...

BACKGROUND: The iron overload condition hereditary hemochromatosis (HH) can cause liver cirrhosis and cancer, diabetes, and arthritis. Males homozygous for the p.C282Y missense mutation in the Homeostatin Iron Regulator (HFE) gene have greatest risk; yet, only a minority develop these conditions. We aimed to determine whether common genetic variants influencing iron levels or liver disease risk in the general population also modify clinical penetrance in HFE p.C282Y and p.H63D carriers...

Cognitive decline of aging is modulated by chronic inflammation and comorbidities. In people with HIV-infection (PWH) it may also be affected by HIV-induced inflammation, lifestyle and long-term effects of antiretroviral therapies (ART). The role of genetics in the susceptibility to HIV-associated neurocognitive disorders (HAND) is not fully understood. Here we explored the possible relations among variants in 3 genes involved in inflammation and neurodegenerative disorders (APOE: ε2/ε3/ε4; HFE: H63D; C9ORF72: hexanucleotide expansions ≥ 9 repeats), cognitive/functional impairment (MiniMental State Examination MMSE, Clock Drawing Test CDT, Short Physical Performance Battery SPPB), comorbidities and HIV-related variables in a cohort of > 50 years old PWH (n = 60) with at least 10 years efficient ART...

Patients with non-transfusion dependent thalassemia (NTDT) develop variable degrees of iron overload. Possible genes which may be implicated in causing iron overload are hepcidin ( HAMP ) and hemojuvelin ( HFE ). There is variable data assessing the role of c.-582Y A  >  G HAMP gene and H63D hotspot in HFE-1 gene in causing iron overload, while role of HFE-2 gene is undetermined. Twenty-five patients with NTDT (≥ 10 years) were assessed for iron overload. Genetic analysis for β-globin, α-globin, HAMP, HFE-2 and C282Y and H63D hotspots in HFE-1 genes was performed...

Increasing evidence supports the potential role of iron metabolism in multiple sclerosis (MS). Previous studies examining the association between polymorphisms of the hemochromatosis gene ( HFE ) and susceptibility to MS have yielded inconsistent results. In the present study, a meta-analysis of 7 studies was performed conducted in populations of Caucasian origin using the Comprehensive Meta-analysis 3.0 software. The strength of association between the C282Y and H63D polymorphisms in HFE and MS risk was estimated by odds ratios with 95% confidence intervals...