scholarly journals Frequency of the Hemochromatosis Gene (HFE) Variants in a Jordanian Arab Population and in Diabetics from the Same Region

2009 ◽  
Vol 27 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Asem Alkhateeb ◽  
Amal Uzrail ◽  
Khaldon Bodoor
Keyword(s):  
Blood Donor ◽  
Hereditary Hemochromatosis ◽  
University Hospital ◽  
European Ancestry ◽  
Hfe Gene ◽  
Arab Population ◽  
Population Type ◽  
Significant Difference ◽  
Hemochromatosis Gene

Hereditary HFE-linked hemochromatosis is a frequent recessive disorder among individuals of northern European ancestry. The clinical characteristic of this disease is the gradual accumulation of iron in internal organs, which ultimately may lead to organ damage and death. Three allelic variants of HFE gene have been correlated with hereditary hemochromatosis: C282Y is significantly associated with hereditary hemochromatosis in populations of Celtic origin, H63D and S65C are associated with milder form of iron overload. In this study we performed mutation analysis to identify allele frequency of the three variants of HFE gene in Jordanian Arab population, to assess deviations of these frequencies from those detected elsewhere, and to determine if there is an increased frequency of these variants in a diabetic population (Type 2 diabetes) from the same area. DNA was extracted from blood samples of 440 individuals attending King Abdullah University Hospital for ambulatory services. We used polymerase chain reaction (PCR) to amplify exons 2 and 4 of the HFE gene then restriction fragment length polymorphism (RFLP) method to detect the variants. There were neither homozygous nor heterozygous for C282Y variant. For the H63D variant, 0.68% were homozygous and 21.1% were heterozygous. For the S65C variant, there were no homozygous and 0.23% were heterozygous. Allelic frequencies were, 0%, 11.25%, and 0.11% for C282Y, H63D, and S65C, respectively. Our samples were subdivided into two categories of type 2 diabetic (89 cases) and controls (blood donors, 204 cases) and compared with regard to the H63D variant. Both groups did not have homozygous H63D variant. H63D heterozygous in diabetics were 23.60% and in blood donor controls 22.55%. Allelic frequency of the mutant H63D allele was 11.80% in diabetics and 11.27% for the blood donor controls. This is the first study to show the frequency of the three hemochromatosis gene variants in Jordan with the interesting finding of no C282Y allele detected in 440 samples. Additionally, no significant difference was observed in H63D variant frequency in type 2 diabetics as compared to controls.

scholarly journals The Frequency of Malnutrition in Patients with Type 2 Diabetes

2021 ◽  
Author(s):  
Miraç Vural Keskinler ◽  
Güneş Feyizoğlu ◽  
Kübra Yıldız ◽  
Aytekin Oğuz
Keyword(s):  
Type 2 Diabetes ◽  
Outpatient Clinic ◽  
High Body Mass Index ◽  
Cross Sectional Study ◽  
University Hospital ◽  
Nutritional Risk ◽  
Cross Sectional ◽  
Significant Difference ◽  
Nrs 2002

Objective: Obesity is one of the most common comorbidities of diabetes mellitus (DM) whose frequency is rapidly increasing nowadays. Although obesity caused by excessive and unbalanced nutrition often accompanies diabetes; malnutrition is another complication of diabetes. This study was conducted to investigate the frequency of malnutrition in individuals with diabetes. Method: This study is a cross-sectional study. The patients with type 2 diabetes followed up in the diabetes outpatient clinic of a university hospital between February and March 2018 were included in the study. Anthropometric measurements of the patients and “Nutritional Risk Screening-2002” (NRS-2002) scores were recorded. Results: A total of 222 (F: 132 59.4%) patients were included in the study. When two groups with higher NRS (≥3) and lower NRS (<3) scores less than 3 were compared, any significant difference was not detected between two groups in terms of age, waist circumference and HbA1c values. Only BMI was found to be lower in the group with malnutrition risk (p: 0.030). When the patients were evaluated in terms of diabetes treatments and risk of malnutrition, any significant intergroup difference was not found (p: 0.847). Conclusion: It was found that there is a risk of malnutrition in one of every seven diabetics with a high body mass index who were being followed up in the diabetes outpatient clinic.

scholarly journals HFE Gene Mutation Status Predicts Response to Gemtuzumab Ozogamicin in AML

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1307-1307 ◽  
Author(s):  
Etienne Paubelle ◽  
Alice Marceau ◽  
Florence Zylbersztejn ◽  
Mickael Dussiot ◽  
Ivan Cruz Moura ◽  
...  
Keyword(s):  
Total Dose ◽  
Conflicts Of Interest ◽  
Hereditary Hemochromatosis ◽  
Gemtuzumab Ozogamicin ◽  
Hfe Gene ◽  
Study Cohort ◽  
Dependent Manner ◽  
Wild Type ◽  
Significant Difference ◽  
Hfe Mutations

Abstract BACKROUND: The protein defective in type 1 hereditary hemochromatosis, called HFE, is similar to MHC class I-type proteins, associates with beta2-microglobulin and is implicated in membranous protein recycling. Gemtuzumab ozogamicin (GO), a monoclonal antibody directed against CD33 linked to a cytotoxic agent, has been used with controversial effects in acute myeloid leukemia (AML). Internalization of GO is required for its anti-leukemic effect. Therefore, we hypothesized that H63D or C282Y HFE gene mutations may impair GO activity by preventing its internalization. METHODS: Wild type, C282Y and H63D HFE leukemic cells and primary cell were used to assess effects of GO alone or in combination with cytarabine on cell proliferation and apoptosis. Flow cytometry, confocal and AMNIS stream analysis were used to evaluate GO internalization. HFE mutations were analyzed by PCR analysis on DNA from patients included in clinical studies. Post-hoc subgroup analysis was performed to assess in vivo the role of HFE status on GO efficacy and toxicity among the 280 patients of the ALFA-0701 study as a study cohort (patients aged 50-70 years; GO 3mg/m² on days 1, 4, and 7 of chemotherapy and on day 1 of the first and second induction ; total dose 15 mg/m² ) and then on the GOELAMS-LAM 2006 IR study (patients aged 18-60 years; GO 6 mg/m² on day 4 of chemotherapy during the induction and the first consolidation; total dose 12 mg/m²) and UK NCRI AML17 study (patients aged 18-81 years; GO 3 vs 6 mg/m² on day 1 of chemotherapy but not during consolidation) as validating cohorts. RESULTS: GO induced cell death by apoptosis in AML cell lines and primary cells in a dose-dependent manner and synergistically in combination with cytarabine. However, the IC5O of GO was significantly higher in HFE mutated cells (125 vs 10 ng/mL p<0.001). To further understand this phenomenon, the CD33 internalization was analyzed upon GO or anti-CD33 antibody exposure. In line with the cytotoxic effect, CD33 was significantly less internalized in HFE mutant cells (17.4% vs 65.1% after 1 hour, p<0.01). HFE mutations were screened in 242 of the 280 ALFA-0701 patients with DNA available. There were 155 non-mutated patients (64%), 68 (28%) heterozygous for H63D, 11 (5%) heterozygous for C282Y, and 8 (3%) homozygous for H63D, which is consistent with the prevalence of the various mutations in the French population. Median age was 62 years (50-71) and the M/F ratio was 0.5, equally distributed among the different groups. No significant difference was observed with respect to the diagnosis of various hematological parameters, including white blood cell count, blasts number, cytogenetic subgroups, molecular mutation incidences (FLT3, NPM1, CEBPA, IDH, DNMT3A). In the ALFA-0701 study cohort, HFE wild-type (WT) patients had a higher overall survival (OS) when treated in the GO arm (median, not reached vs 19.5 months, p=0.0193). In contrast, OS was similar among patients with heterozygotes HFE mutations treated in the GO and the control arm (median, 19.9 vs 21.9, p=0.9675). In confirmatory cohorts, GO treatment led to a trend to increased OS in the GOELAMS-LAM 2006 IR cohort only in HFE WT patients (4-year OS with GO 62% vs 48%, p=0.08) but not in mutated patients (4-year OS with GO 73% vs 64%, p=0.45). Furthermore, in this cohort in the FLT3 WT patients subgroup, GO further improve OS in WT patients (4-year OS with GO 72% vs 50%, p=0.017), but not in patients with heterozygous HFE mutation (4-year OS with GO 80% vs 65%, p=0.23) In the UK NCRI AML17 cohort, which used GO only during induction, 245 patients were randomized between GO at 3mg/m2 and 6mg/m2 and evaluated for HFE status. Overall there was no effect of GO dose on outcomes, and no evidence of either any heterogeneity by HFE, nor any subgroup, which showed a differential effect of GO dose. CONCLUSIONS: Future studies should focus on optimising the fractionated schedule for GO at the 3mg/m2. Fractionated high doses (3x3mg/m2) during induction and single dose during consolidation seems to be the best schedule. Most importantly, the effect of GO treatment differed between HFE WT and heterozygote mutated AML patients. GO only increased OS among HFE WT patients. This is likely related to impaired internalization of the CD33 target. Our data suggest that HFE status should be used as a companion test to predict outcome of AML treated with GO. Disclosures No relevant conflicts of interest to declare.

Physiology of iron transport and the hemochromatosis gene

2002 ◽  
Vol 282 (3) ◽  
pp. G403-G414 ◽  
Author(s):  
Antonello Pietrangelo
Keyword(s):  
Iron Homeostasis ◽  
Cell Damage ◽  
Hereditary Hemochromatosis ◽  
Hfe Gene ◽  
Cell Functions ◽  
Cellular Iron ◽  
Histocompatibility Complex ◽  
Biological Studies ◽  
Hemochromatosis Gene ◽  
Main Protein

Iron is essential for fundamental cell functions but is also a catalyst for chemical reactions involving free radical formation, potentially leading to oxidative stress and cell damage. Cellular iron levels are therefore carefully regulated to maintain an adequate substrate while also minimizing the pool of potentially toxic “free iron.” The main control of body iron homeostasis in higher organisms is placed in the duodenum, where dietary iron is absorbed, whereas no controlled means of eliminating unwanted iron have evolved in mammals. Hereditary hemochromatosis, the prototype of deregulated iron homeostasis in humans, is due to inappropriately increased iron absorption and is commonly associated to a mutated HFE gene. The HFE protein is homologous to major histocompatibility complex class I proteins but is not an iron carrier, whereas biochemical and cell biological studies have shown that the transferrin receptor, the main protein devoted to cellular uptake of transferrin iron, interacts with HFE. This review focuses on recent advances in iron research and presents a model of HFE function in iron metabolism.

scholarly journals Complete Scanning of the Hereditary Hemochromatosis Gene (HFE) by Use of Denaturing HPLC

2001 ◽  
Vol 47 (9) ◽  
pp. 1633-1640 ◽  
Author(s):  
Gerald Le Gac ◽  
Catherine Mura ◽  
Claude Férec
Keyword(s):  
Hereditary Hemochromatosis ◽  
Hfe Gene ◽  
Test Accuracy ◽  
Melting Profile ◽  
Coding Region ◽  
Hemochromatosis Gene ◽  
Hfe Mutations ◽  
Methods Analytical ◽  
Positive Controls ◽  
Experimental Melting

Abstract Background: Between 4% and 35% of hereditary hemochromatosis (HC) probands are C282Y or H63D heterozygotes or lack both of these two common HFE mutations, and 15 novel HFE mutations have been described recently. We evaluated denaturing HPLC (DHPLC) for screening of the whole HFE coding region and further defined whether HC probands with an incomplete HFE genotype carry uncommon mutations. Methods: Analytical conditions for each coding exon were determined by a combination of computer melting profile predictions and experimental melting curves. To test accuracy for scanning the complete HFE coding region and optimize DHPLC running conditions, each melting domain was investigated with at least one mutation or one polymorphism as reference. We tested 100 DNA samples harboring the C282Y, H63D, or S65C mutations and 17 artificially created positive controls that carried either 1 of the 14 other known HFE mutations or 3 selected polymorphisms. Results: Investigations on each of the coding exons 1, 2, 4, 5, and 6 could be performed at one analysis temperature. Coding exon 3 displayed a more complex melting profile and required two analysis temperatures. DHPLC detected all known HFE mutations as well as the three selected polymorphisms. Conclusions: DHPLC can be used to scan the HFE gene in HC probands in whom at least one chromosome lacks an assigned mutation.

The effect of family support and family conflict on treatment compliance in type 2 diabetes

2020 ◽  
Vol 10 (2) ◽  
pp. 48-54
Author(s):  
S. Hançerlioğlu ◽  
İ. Toygar ◽  
N. Çıray ◽  
G. Polat ◽  
Y. Özbey ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Family Support ◽  
Family Conflict ◽  
Treatment Compliance ◽  
University Hospital ◽  
Patient Identification ◽  
Hospital Data ◽  
Type 2 Dm ◽  
Significant Difference

Purpose: To evaluate the effect of family support and family conflict on treatment compliance of type 2 diabetes patients. Materials/Methods: The study was conducted in the endocrinology department of a university hospital. Data were collected from 174 individuals diagnosed with Type 2 DM. Patient Identification Form, Family Support and Conflict Scale in Type 2 Diabetes, and Patient Compliance Scale in Type 2 DM Treatment were used for data collection. Results: It was found that the increase in family support increased compliance with the treatment, and the increase in family conflict decreased the compliance to the treatment. A statistically significant difference was found between gender (p = 0.037), place of residence (p <0.001), income level (p <0.001) and compliance. A statistically significant difference was found between marital status (p <0.001) and family support. Conclusions: The increase in family support increases compliance to the treatment, the increase in family conflict decreases the compliance to the treatment.

Recommendation of Aspirin-Guide App and Physicians Clinical Decision of Aspirin Use to Prevent CVD Among Diabetic Patients, Is there any Differences?

2020 ◽  
pp. 107424842095897
Author(s):  
Mohammed Ali Batais ◽  
Khalid M. Almutairi ◽  
Turky H. Almigbal ◽  
Abdulaziz Alodhayani ◽  
Wadi B. Alonazi ◽  
...  
Keyword(s):  
Clinical Decision ◽  
Cross Sectional Study ◽  
Aspirin Therapy ◽  
Mobile App ◽  
University Hospital ◽  
Diabetic Patients ◽  
Patient Acceptability ◽  
Cross Sectional ◽  
Significant Difference

Objective: This study aims to identify the prevalence of aspirin use among type 2 diabetic (T2DM) patients and assess the concordance in aspirin use among these patients as prescribed by physicians and as recommended by the Aspirin-Guide app. Methods: A total of 301 T2DM patients from King Khalid University Hospital in Riyadh, Saudi Arabia participated in this cross-sectional study. Patient’s electronic medical records through eSihi system were reviewed and all data included in the free online and mobile app called Aspirin-Guide were collected in a specially designed data checklist. Result: The prevalence of aspirin use was more common in patients who were in the age group of 51 to 59 and male participants’ with T2DM. Males were nearly twice more likely to use aspirin compared to females (p = 0.001). Based on recommendations from the Aspirin-Guide app, 26% of the patients who were on aspirin (N = 51) were not eligible for aspirin therapy, while 37.7% (N = 40) of the patients eligible for aspirin therapy had not been put on aspirin by their physicians (p = 0.039). Male sex (P = 0.003), use of statins (P = 0.001), and being advised to use aspirin (P = 0.041), were significantly associated with aspirin use in T2DM patients. Conclusion: There was a significant difference in the proportion of patients currently on aspirin as prescribed by their physicians and those eligible for aspirin therapy as per the Aspirin-Guide app. The use of an app to uniformized aspirin use among eligible patients should be based on up-to-date guidelines and account for patient acceptability and willingness to commence treatment.

scholarly journals Clinical and Biochemical Predictors of Endothelial Dysfunction in Egyptian Adolescents with Type 1 and those with Type 2 Diabetes

2021 ◽  
pp. 87-97
Author(s):  
EkramHamed Zakaria ◽  
MedhatAbdElmaged Ghazy ◽  
Wesam Salah Mohamed ◽  
Nesreen Ahmed Kotb
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
University Hospital ◽  
Control Group ◽  
Model Assessment ◽  
Significant Difference

Aims: Since endothelial dysfunction precedes clinically significant diabetic vascular complications, circulating endothelial progenitor cells (EPCs) have generated interest as a biomarker of endothelial function and are considered a mirror for endogenous vasculo-regenerative capacity. So we aimed to assess EPCs count in adolescents with type 1 diabetes mellitus (T1DM) in comparison to those with type 2 diabetes mellitus (T2DM) and extend these findings to assess their relationship to other clinical and biochemical risks of endothelial dysfunction. Patients and Methods: Fifty Egyptian adolescents were included in this study, 20 with T1DM, 20 T2DM and 10 healthy control subjects. Patients are recruited from Diabetes and Endocrinology Unit, outpatient clinic of internal medicine department Tanta University Hospital, in the period from 2017 to 2019. EPCs count was determined by Flowcytometry, anthropometric measurements and laboratory investigations were done for fasting and 2-hours post-prandial blood glucose, serum lipid profile, HbA1c, urinary albumin creatinine ratio, fasting C peptide, and homoeostasis model assessment of insulin resistance (HOMA- IR). Results: In T1DM, EPCs count was significantly higher compared to T2DM(0.032) and control group(p0.001) and it was negatively correlated with age of patients and duration of diabetes but was positively correlated with HbA1c. While, the count was higher in T2DM compared to control with no statistically significant difference(p0.063) and negatively correlated with body mass index, waist circumference, blood pressure and HOMA-IR. Conclusion: Adolescents with T2DM have distressing clinical and biochemical findings and significantly lower count of (EPCs) than adolescents with T1DM. This puts them at potential higher risk for early development of endothelial dysfunction and less power of vascular repair that may potentiate early harboring of vascular complications.

scholarly journals C282Y and H63D Mutation Frequencies in a Population from Central Spain

2001 ◽  
Vol 17 (2) ◽  
pp. 111-114 ◽  
Author(s):  
S. Alvarez ◽  
M. S. Mesa ◽  
F. Bandrés ◽  
E. Arroyo
Keyword(s):  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Epidemiological Data ◽  
Hfe Gene ◽  
Mediterranean Populations ◽  
H63d Mutation ◽  
Pcr Rflp ◽  
Hemochromatosis Gene ◽  
Ethidium Bromide Staining ◽  
Spanish Populations

Objectives:To determine the frequency of hereditary hemochromatosis gene mutations, C282Y and H63D, from 125 autochthonous blood donors originating from a Central region of Spain, to provide epidemiological data about HFE gene in the Iberian Peninsula.Methods:DNA extracted from blood samples was analyzed by PCR-RFLP. Restriction enzimes were Snab I and Bcl I for C282Y and H63D, respectively. Results were visualized with Ethidium Bromide staining after gel electrophoresis.Results and discussion:C282Y frequency was 0.02 and that of H63D was 0.16. Result for C282Y mutation falls within the range of variation of the Mediterranean populations. H63D frequency agrees with those reported for other European populations. In both cases frequencies obtained are the lowest of compared Spanish data.Conclusions:This study is useful to compare expected versus presented C282Y and H63D frequencies in Spanish populations and to contribute to the knowledge of Spanish variability, rarely analyzed until now for HFE gene mutations.

HIP FRACTURES IN 5 YEARS AT HUE UNIVERSITY HOSPITAL

2014 ◽  
pp. 47-50
Author(s):  
Duy Binh Ho ◽  
Nghi Thanh Nhan Le ◽  
Maasalu Katre ◽  
Koks Sulev ◽  
Märtson Aare
Keyword(s):  
Hip Fracture ◽  
Femoral Neck ◽  
Hip Fractures ◽  
Age Groups ◽  
Femoral Fractures ◽  
Femoral Neck Fractures ◽  
University Hospital ◽  
High Risk Population ◽  
Intertrochanteric Fractures ◽  
Significant Difference

Aim: This study aimed to review the clinical findings and surgical intervention of the hip fracture at the Hue University Hospital in Vietnam. Methods:The data of proximal femoral fractures was collected retrospectively. All patients, in a period of 5 years, from Jan 2008 to December 2012, suffered either from intertrochanteric or femoral neck fractures. The numbers of patients were gathered separately for each year, by age groups (under 40, 40-49, 50-59, 60-69, 70-79, older) and by sex. We analyzed what kind of treatment options were used for the hip fracture. Results:Of 224 patients (93 men and 131 women) studied, 71% patients are over 70 years old, 103 women and 56 men (p<0.05). For patients under 40 years, there were 1 woman and 11 men (p<0.05). There were 88 intertrochanteric and 136 femoral neck fractures. There was no significant difference in the two fractures between men and women. The numbers of hip fracture increased by each year, 29/224 cases in 2010, 63/224 cases in 2011, 76/224 cases in 2012. Treatment of 88 intertrochanteric fractures: 49 cases (55.7%) of dynamic hip screw (DHS), 14 cases of hemiarthroplasty (15.9%), 2 cases of total hip replacement (2.3%). Treatment of 136 femoral neck fractures: 48 cases of total replacement (35.3%), 43 cases of hemiarthroplasty (31.6%), 15 cases of screwing (11%). In cases of 40 patients (17.9%) hip fracture was managed conservatively, 23 were femoral neck fractures and 17 were intertrochanteric fractures. Conclusions: Hip fracture is growing challenge in Hue medical university hospital. The conservative approach is still high in people who could not be operable due to severe medical conditions as well as for patients with economic difficulties. Over 70% of the hip fractures in people 70+ are caused by osteoporosis. The number of hip fracture is increasing in the following years, most likely due to the increase in the prevalence of osteoporosis. Early detection and prevention of osteoporosis should be addressed, particularly in high risk population. More aggressive surgical approach should be implemented in order to improve the quality of life in patients with hip fractures. Key words:Hip fracture.

scholarly journals DARAPLADIB INHIBIT ADHESION MOLECULE EXPRESSION IN AORTA AT EARLY STAGES OF ATHEROSCLEROSIS USING SPRAGUE-DAWLEY TYPE 2 DIABETES MELLITUS MODEL

2017 ◽  
Vol 10 (6) ◽  
pp. 373 ◽  
Author(s):  
Heriansyah T ◽  
Hanifa H ◽  
Andarini S ◽  
Wihastuti Titin Andri
Keyword(s):  
Diabetes Mellitus ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Fasting Blood Glucose ◽  
Sprague Dawley ◽  
Nonesterified Fatty Acids ◽  
Early Stages ◽  
Significant Difference ◽  
Atherosclerosis Treatment

Objective: Hyperglycemia and hyperlipidemia in diabetes mellitus (DM) can lead an atherosclerosis. The increase of low-density lipoprotein level in DM and atherosclerosis is correlated with lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids. LysoPC regulated inflammation mediators, include cytokines, adhesion molecules (such as vascular cell adhesion molecule-1 [VCAM-1] and intercellular adhesion molecules-1 [ICAM-1]), and monocyte chemoattractant protein-1 (MCP-1) chemotactic. Darapladib is known as a Lp-PLA2 specific inhibitor. It is also considered to be an atherosclerosis treatment. The aim of this study is to know darapladib effect on VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague-Dawley Type 2 DM (T2DM) model.Methods: About 30 Spraque-Dawley rats are divided into three main groups: Normal, T2DM, and T2DM with darapladib administration group. Each group consists of 2 serials treatment time: 8 and 16 weeks treatment group. Fasting blood glucose, resistance insulin, and lipid profile were measured and analyzed to ensure T2DM model. VCAM-1 and ICAM-1 expression were measured using double staining immunofluorescence. Each data were analyzed using one-way ANOVA.Results: There is a significant difference in VCAM-1 expression in T2DM group (8 and 16 weeks), with p=0.011 and 0.034 (p<0.05), respectively. Mean while, a significant difference for ICAM-1 only showed in 8 weeks T2DM group with p=0.03 (p<0.05). Moreover, there is a decreasing trend in 16 weeks T2DM group.Conclusion: Our results showed that darapladib can decrease VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague- Dawley T2DM model. This showed another evidence of darapladib as atherosclerosis treatment.

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