Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemochromatosis is one of the most frequent genetic diseases among the white populations, affecting one in three hundred persons. Its diagnosis has been radically transformed by the discovery of the HFE gene. In a given individual, the diagnosis can, from now on, be ascertained on the sole association of a plasma transferrin saturation (TS) over 45% and homozygosity for the C282Y mutation. Liver biopsy is only required to search for cirrhosis whenever there is hepatomegaly and/or serum ferritin >1000 ng/ml and/or elevated serum AST. Family screening is mandatory, primarily centered on the siblings. The treatment remains based on venesection therapy which improves many features of the disease (one of the most refractory, however, being the joint signs) and permits normal life expectancy provided the diagnosis is established prior to the development of cirrhosis or of insulin-dependent diabetes. In view of the prevalence, the non-invasive diagnosis, the spontaneous severity and the efficacy of a very simple therapy, hemochromatosis should benefit from population screening. This screening could be based, first, on the assessment of transferrin saturation, followed - when elevated - by the search for the C282Y mutation. The discovery of the HFE gene has also paved the road for the individualization of other types of iron overload syndromes which are not HFE-related.
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PMID:Clinical aspects of hemochromatosis. 1109 95

Multiple factors appear to be involved in the pathogenesis of type 2 (non insulin dependent) diabetes mellitus (DM). One of these factors may be iron overload. This critical review summarizes the major studies on the link between type 2 DM, insulin resistance, glycemic control, diabetic complications and hyperferritinemia. Although some studies suggested that plasma ferritin concentration is positively correlated with insulin resistance and with the risk of acquiring type 2 DM, substantial iron overload is not a typical feature of DM. There is no correlation between plasma ferritin level and glycemic control or diabetic microangiopathic complications.
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PMID:Plasma ferritin and type 2 diabetes mellitus: a critical review. 1142 24

The efficacy of insulin in stimulating whole-body glucose disposal (insulin sensitivity) was quantified using direct methodology in thirty lacto-ovo vegetarians and in thirty meat-eaters. All subjects were adult, lean (BMI <23 kg/m2), healthy and glucose tolerant. Lacto-ovo vegetarians were more insulin sensitive than meat-eaters, with a steady-state plasma glucose (mmol/l) of 4.1 (95 % CI 3.5, 5.0) v. 6.9 (95 % CI 5.2, 7.5; respectively. In addition, lacto-ovo vegetarians had lower body Fe stores, as indicated by a serum ferritin concentration (microg/l) of 35 (95 % CI 21, 49) compared with 72 (95 % CI 45, 100) for meat-eaters To test whether or not Fe status might modulate insulin sensitivity, body Fe was lowered by phlebotomy in six male meat-eaters to levels similar to that seen in vegetarians, with a resultant approximately 40 % enhancement of insulin-mediated glucose disposal Our results demonstrate that lacto-ovo vegetarians are more insulin sensitive and have lower Fe stores than meat-eaters. In addition, it seems that reduced insulin sensitivity in meat-eaters is amenable to improvement by reducing body Fe. The latter finding is in agreement with results from animal studies where, no matter how induced, Fe depletion consistently enhanced glucose disposal.
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PMID:Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians. 1159 Dec 39

Insulin resistance syndrome (IRS) is a cluster of prevalent conditions including glucose intolerance, hypertension and dyslipidemia, which commonly predispose to cardiovascular disease. However, the mechanism by which IRS is related with cardiovascular disease is not yet settled. Recently, it has been hypothesized that atherosclerosis is an inflammatory disease and that an increase in oxidative stress plays a key role in causing endothelial dysfunction associated with atherosclerosis. There has been, however, no study directly relating IRS with oxidative stress in human subjects. We measured various markers of oxidative stress among subjects who participated in a population-based epidemiological study performed in 1996. IRS was defined as non-diabetic subjects having more than two of three salient features of the syndrome (glucose intolerance, hypertriglyceridemia/low high density lipoprotein (HDL)-cholesterol and hypertension). The subjects with IRS (n=70) showed higher plasma malondialdehyde (MDA; 2.10+/-1.43 vs. 1.63+/-1.21 micromol/ml, P=0.009), homocysteine (16.32+/-8.34 vs. 13.06+/-6.49 micromol/l, P=0.002) and ceruloplasmin concentrations (29.80+/-5.28 vs. 27.39+/-5.10 mg/dl, P=0.002) than control subjects (n=196). Plasma MDA concentration was positively correlated with waist-to-hip ratio (r=0.124, P=0.044), and with plasma triglyceride (TG; r=0.163, P=0.008), ferritin (r=0.200, P=0.002) and homocysteine concentrations (r=0.136, P=0.032). These results suggest that increase in oxidative stress may contribute to the development of cardiovascular disease in IRS.
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PMID:Oxidative stress markers in Korean subjects with insulin resistance syndrome. 1173 6

The aim of this study was to compare the frequencies of HFE mutations in African-American women with non-insulin-dependent diabetes mellitus (NIDDM) to that of controls and to determine whether these mutations are associated with NIDDM and iron overload. We studied 167 African-American women with NIDDM. The 71 non-diabetic controls were African-American female controls. HLA-A and -B typing and HFE mutation analysis for C282Y and H63D alleles were performed using standard molecular genetic techniques. The frequencies of C282Y and H63D were not significantly different in NIDDM patients and controls. C282Y was observed in 0.59% of patients and 1.41% of controls. H63D was observed in 2.99% of patients and 3.08% of controls. All of the NIDDM patients who possessed either C282Y or H63D mutations had normal values of serum ferritin, serum iron and transferrin saturation. A woman who inherited C282Y also possessed HLA-A3, -B7 which is considered part of the ancestral haplotype containing the gene predisposing to hemochromatosis in Caucasians. The frequencies of C282Y and H63D vary in African Americans from different geographic regions of the United States; this variance can be explained by Caucasian admixture. Although most iron overload cases in African Americans bear more resemblance to cases of African iron overload than to those of Caucasian hemochromatosis, rare cases resembling Caucasian hemochromatosis have been observed in African Americans.
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PMID:HFE mutations in African-American women with non-insulin-dependent diabetes mellitus. 1176 82

The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.
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PMID:A homozygous HFE gene splice site mutation (IVS5+1 G/A) in a hereditary hemochromatosis patient of Vietnamese origin. 1187 12

Iron-related insulin-resistance is improved by iron depletion or treatment with iron chelators. The aim of this study was to evaluate insulin sensitivity and insulin secretion after blood letting in patients who had high-ferritin type 2 diabetes and were randomized to blood letting (three phlebotomies [500 ml of blood] at 2-week intervals, group 1) or to observation (group 2). Insulin secretion and sensitivity were tested at baseline and 4 and 12 months thereafter. The two groups were matched for age, BMI, pharmacologic treatment, and chronic diabetic complications. All patients were negative for C282Y mutation of hereditary hemochromatosis. Baseline glycated hemoglobin (6.27 +/- 0.9% vs. 6.39 +/- 1.2%), insulin sensitivity (2.75 +/- 1.8 vs. 3.2 +/- 2.1 mg.dl(-1).min(-1)), and area under the curve for C-peptide (AUC(C-peptide); 38.7 +/- 11.6 vs. 37.6 +/- 14.1 ng.ml(-1).min(-1)) were not significantly different between the two groups of patients. Body weight, blood pressure, blood hematocrit levels, and drug treatment remained essentially unchanged during the study period. As expected, serum ferritin, transferrin saturation index, and blood hemoglobin decreased significantly at 4 months only in patients who received blood letting. In parallel to this changes, blood HbA(1c) decreased significantly only in group 1 subjects (mean differences, -0.61; 95% CI, -0.17 to -1.048; P = 0.01). AUC(C-peptide) decreased by -10.2 +/- 6.3% after blood letting. In contrast, a 10.4 +/- 6.4% increase in AUC(C-peptide) was noted in group 2 subjects at 4 months (P = 0.032). At 12 months, AUC(C-peptide) returned to values not significantly different from baseline in the two groups of subjects. At 4 months, the change in insulin sensitivity from baseline was significantly different between the two groups (80.6 +/- 43.2% vs. -8.6 +/- 9.9% in groups 1 and 2, respectively, P = 0.049). At 12 months, the differences between the two groups were even more marked (55.5 +/- 24.8% vs. -26.8 +/- 9.9%; P = 0.005). When the analysis was restricted to those subjects who completed the follow-up until 12 months, results did not show differences compared with the changes observed at 4 months, except for insulin sensitivity. A statistically significant increase in insulin sensitivity was observed in the blood-letting group (from 2.30 +/- 1.81 to 3.08 +/- 2.55 mg.dl(-1).min(-1) at 4 months, to 3.16 +/- 1.85 mg.dl(-1).min(-1) at 12 months; P = 0,045) in contrast with group 2 subjects (from 3.24 +/- 1.9 to 3.26 +/- 2.05 mg.dl(-1).min(-1) at 4 months, to 2.31 +/- 1.35 mg.dl(-1).min(-1) at 12 months). In summary, blood letting led simultaneously to decreased blood HbA(1c) levels and to changes in insulin secretion and insulin resistance that were significantly different from those observed in a matched observational group of subjects with high-ferritin type 2 diabetes. The mechanisms for improvement in peripheral insulin sensitivity after blood letting should be investigated further.
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PMID:Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function. 1191 18

Iron is an important factor in the process of oxidation stress and atherogenesis which is as a rule potentiated in subjects with the insulin resistance syndrome. Hypertension is one of the main components of this syndrome. Ferritin due to its relationship with impaired insulin sensitivity becomes a candidate for a new indicator of insulin resistance. The subject of the present study was to assess whether we shall find in young healthy offspring of hypertensive parents changes in the ferritin level, oxidizability of LDL and whether these are related to parameters of glucose tolerance, insulin secretion and sensitivity. Twelve young (27 +/- 3.6 years) non-obese, normotesive offspring of hypertensive parents were compared with a group of 14 controls. Glucose tolerance, insulin secretion and sensitivity were examined by means of a hyperglycaemic clamp and oGTT. As to the ferritin level, the offspring of hypertensive parents did not differ significantly from controls, differences were not fond in the oxidizability of LDL-C. The glucose tolerance was comparable in the two groups. Offspring of hypertensive parents had however a significantly higher insulin and C peptide level when using the clamp and during the glucose tolerance test (p < 0.05), and a reduced insulin sensitivity (p < 0.05). The negative correlation between the index of insulin sensitivity and ferritin suggests that ferritin could be associated with the syndrome of insulin resistance.
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PMID:[Serum ferritin, LDL oxidation and risk factors for atherogenesis in healthy offspring of hypertensive patients]. 1194 17

Controversy surrounds the role of iron (Fe) in atherosclerosis (ASCVD), mainly due to the inaccuracy of assessing body Fe stores with serum ferritin and transferrin saturation. Quantitative phlebotomy was used to test whether or not (a) Fe stores are increased in individuals at high risk for ASCVD and (b) Fe depletion to near-deficiency (NID) levels is associated with reduction of risk factors for ASCVD. Thirty-one carbohydrate-intolerant subjects completed the study. Fe stores were within normal limits (1.5 +/- 0.1 g). At NID, a significant increase of HDL-cholesterol (p < 0.001) and reductions of blood pressure (p < 0.001), total and LDL-cholesterol (p < 0.001), triglyceride (p < 0.001), fibrinogen (p < 0.001) and glucose and insulin responses to oral glucose loading (p < 0.001) were noted, while homocysteine plasma concentration remained unchanged. These effects were largely reversed by a 6-month period of Fe repletion with reinstitution of Fe sufficiency. Thus, although individuals at high risk for ASCVD are not Fe-overloaded, they seem to benefit, metabolically and hemodynamically, from lowering of body Fe to levels commonly seen in premenopausal females.
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PMID:Effect of iron depletion on cardiovascular risk factors: studies in carbohydrate-intolerant patients. 1207 62

The adipocyte-derived hormone, leptin, has been implicated in the regulation of appetite, weight gain and glucose homeostasis as well as in liver fibrogenesis, hematopoiesis and immune function. No previous reports have clearly defined pathologically elevated or decreased serum leptin levels for Caucasian adults. The aim of this study was to define and characterize subjects with relative hyper- and hypoleptinemia in a large population-based German cohort. Percentiles of leptin levels by body mass index (BMI) were calculated from 4971 adult Germans, and the participants with leptin levels above the 95th and below the 5th percentile were defined as relatively hyperleptinemic and relatively hypoleptinemic, respectively, for their BMI. These participants were compared with the intermediate group with respect to anthropometric and clinical data and parameters of glucose and iron metabolism, lipid status, renal, adrenal and reproductive function. Relatively hyperleptinemic participants (HL) showed higher insulin, c-peptide, and total cholesterol levels than the hypoleptinemic subjects; in males, ferritin levels were higher and testosterone levels lower in the HL group. In conclusion, we report the first percentile curves for serum leptin by BMI in a large Caucasian population. Relatively low leptin values may be associated with a lower metabolic risk than relatively high serum leptin values.
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PMID:Definition and characterization of relative hypo- and hyperleptinemia in a large Caucasian population. 1247 85


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