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ABSTRACT: In an animal model VLDL-triglyceride secretion is highly dependent on stearoyl-coA desaturase (SCD) activity and could explain abdominal fattening. The aim was to assess the relationship of plasma palmitoleic acid content, a product of SCD activity, with triglyceridemia and abdominal adiposity in humans.
We evaluated 134 healthy men. Plasma palmitoleic acid content was used as an indirect measurement of SCD activity because that enzyme catalyzes the desaturation from saturated to monounsaturated fatty acids and palmitoleic acid intake is very small.
Subjects with triglycerides > or =75th percentile had a higher palmitoleic acid content than those with triglycerides <75th percentile (3.8+/-0.8 vs 2.8+/-0.9%, p<0.0001). Triglyceridemia was strongly correlated with palmitoleic acid content (PAC) (r=0.533, p<0.001). Mean triglyceridemia was 114% higher (1.43+/-0.75 vs 0.67+/-0.22 mmol/l) in the fourth quartile than in the first quartile of palmitoleic acid content. In a stepwise logistic regression analysis, palmitoleic acid content was the most strongly and independently associated parameter with triglyceridemia, and also with waist circumference when triglyceridemia was not included in the analysis.
Plasma palmitoleic acid content, a product of SCD activity, is an independent marker of triglyceridemia and abdominal adiposity in men. This enzyme (SCD) could represent a target for prevention and treatment of these metabolic disorders in particular in subjects at risk of developing a metabolic syndrome.
Nutrition, metabolism, and cardiovascular diseases: NMCD 08/2008; 18(6):436-40. · 3.52 Impact Factor
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ABSTRACT: In HFE-related haemochromatosis, a large proportion of C282Y homozygotes, especially women, are not detected by phenotypic screening using transferrin saturation. The aim of this study was to identify the clinical and biochemical factors associated with non-expression of the disease as defined as transferrin saturation <45%.
The study was performed in 78 (57 women and 21 men) C282Y homozygotes identified through a large-scale screening program conducted on 19,644 French subjects. Biometric, clinical and biochemical variables including those susceptible to influence body iron stores were tested for association with transferrin saturation levels <45%.
Non-expression was observed in 26/57 (46%) women and in 5/21 (24%) men. At multivariate analysis, female gender (OR: 16.5, 95%CI 1.8-146.5; P = 0.012), body mass index (OR: 1.21, 95%CI 1.02-1.44; P = 0.027), haemoglobin levels (OR: 0.88, 95%CI 0.81-0.97; P = 0.012) and serum ferritin levels (OR: 0.99, 95%CI 0.98-1.00; P = 0.007) were significantly and independently associated with a non-expressing phenotype.
Excess body mass is commonly associated with the lack of phenotypic expression in detected C282Y homozygotes. This should be kept in mind with respect to the design and cost-effectiveness of phenotypic screening programs for haemochromatosis.
Journal of Hepatology 01/2006; 43(6):1055-9. · 9.26 Impact Factor
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ABSTRACT: Dietary habits play a major role in cardiovascular disease risk but few simple nutrition assessment tools are available for clinical practice. We developed a 14-item food frequency questionnaire to evaluate dietary patterns in relation with coronary risk in a French population.
This food frequency questionnaire gave different scores of intake: saturated fatty acids (six questions), mono-unsaturated fatty acids, Omega-3 and Omega-6/Omega-3 polyunsaturated fatty acids (five questions), and fruits and vegetables (three questions). Validity was assessed against a 7-day dietary history (n = 49 subjects) and against biomarkers (n = 181). The food frequency questionnaire was also administered twice with an interval of 15 days to evaluate its reproducibility (n = 20).
Validity against dietary history was assessed with Spearman correlation coefficients which ranged from 0.47 (fruits and vegetables) to 0.63 (polyunsaturated fatty acids/saturated fatty acids) (all P < 0.05), with a mean value of 0.54. On average, 39% of the subjects were classified in the same quartile with the food frequency questionnaire and the dietary history and 84% in the same or adjacent quartile. Biomarker-based validity using Spearman correlation coefficients varied from 0.21 (saturated fatty acids) to 0.53 (Omega-3 polyunsaturated fatty acids) (all P < 0.05), with a mean value of 0.35. On average, 37% of the participants were classified in the same quartile with the food frequency questionnaire and the corresponding biomarkers and 73% in the same or adjacent quartile. Reproducibility assessed by the intraclass correlation coefficient ranged from 0.71 (mono-unsaturated fatty acids) to 0.93 (global score), with a mean value of 0.81.
We validated a short food frequency questionnaire for dietary pattern assessment in coronary prevention.
European Journal of Cardiovascular Prevention and Rehabilitation 12/2005; 12(6):587-95. · 2.63 Impact Factor
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Caroline Le Lan,
Olivier Loréal,
Tally Cohen,
Martine Ropert,
Hava Glickstein,
Fabrice Lainé, Michel Pouchard,
Yves Deugnier,
André Le Treut,
William Breuer,
Z Ioav Cabantchik,
Pierre Brissot
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ABSTRACT: Labile plasma iron (LPI) represents the redox active component of non-transferrin-bound iron (NTBI). Its presence in thalassemic patients has been recently reported. The aim of the present study was to quantify LPI in HFE genetic hemochromatosis (GH) and to characterize the mechanisms accounting for its appearance. We studied 159 subjects subdivided into the following groups: (1) 23 with iron overloaded GH; (2) 14 with iron-depleted GH; (3) 26 with dysmetabolic hepatosiderosis; (4) 33 with alcoholic cirrhosis; (5) 63 healthy controls. Both NTBI and LPI were substantially higher in patients with iron-overloaded GH than in those with iron-depleted GH or in healthy controls. LPI was significantly correlated with serum transaminase increase in this group. LPI was elevated in the alcoholic cirrhosis subgroup of severely affected patients. LPI was found essentially when transferrin saturation exceeded 75%, regardless of the etiologic condition. Transferrin saturation above 75% was related to iron overload in GH and to liver failure in alcoholic cirrhosis. LPI is present in C282Y/C282Y hemochromatosis and may be a marker of toxicity due to its potential for catalyzing the generation of reactive oxygen radicals in vivo.
Blood 07/2005; 105(11):4527-31. · 9.90 Impact Factor
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ABSTRACT: The aim of the study was to simplify the first Sigma erythrocyte sedimentation rate (ESR) method (manual hematocrit adjustment to 0.35, sum of 4 sedimentation levels) and to confirm its clinical relevance. The erythrocyte sedimentation rate of undiluted blood samples from 576 patients was measured simultaneously with and without manual hematocrit adjustment to 0.35 to identify an approximate expression of the area under the curve and a formula for calculating the Sigma ESR. The Sigma ESR formula was based on the sum of 2 unadjusted sedimentation levels, at 30 and 60 minutes, together with the hematocrit value and the hemoglobin concentration. Sigma ESR values in 274 healthy subjects showed a gaussian distribution, no difference between men and women, and no significant increase with age. In recent-onset arthritis or disk-related lumbosciatic syndrome, Sigma ESR seemed to be a more reliable marker of inflammation than the Westergren ESR and C-reactive protein. We also obtained data clarifying the controversial relationship of ESR with lipid levels and arterial hypertension.
American Journal of Clinical Pathology 12/2004; 122(5):802-10. · 2.60 Impact Factor
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ABSTRACT: A decrease in serum ceruloplasmin (Cp), a protein involved in iron metabolism through its ferroxidase activity, is classically claimed to be observed in severe hepatic failure of non-wilsonian chronic liver disease and therefore to be a confounding factor for the diagnosis of Wilson's disease. Moreover, a simultaneous decrease in ferroxidase activity could be hypothesized as playing a role in the development of the hepatic siderosis frequently observed in advanced chronic liver diseases. The aim of this study was to test the validity of these two statements.
This study investigated Cp, determined by immunonephelometry, and its ferroxidase 1 activity determined by Erel's method in 33 male patients with severe alcoholic cirrhosis compared with 66 healthy male volunteers, selected on strict criteria. Each patient was age-matched with two controls. Nonparametric tests were used for statistical analysis.
The mean values of Cp were significantly higher in cirrhotic patients as compared with control subjects. A significant elevation of Cp was also observed in the subgroup of 11 cirrhotic patients who had normal serum C-reactive protein levels. The mean values of ferroxidase 1 activity were similar to those obtained in control subjects.
Low serum Cp should not be expected in severe hepatic cirrhosis of non-wilsonian origin. Hepatic siderosis in advanced chronic liver disease is likely to be unrelated to decreased ferroxidase activity.
Alcoholism Clinical and Experimental Research 06/2004; 28(5):775-9. · 3.34 Impact Factor
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Yves Deugnier,
Anne-Marie Jouanolle,
Jacques Chaperon,
Romain Moirand,
Catherine Pithois,
Jean-François Meyer, Michel Pouchard,
Bernard Lafraise,
Alain Brigand,
Céline Caserio-Schoenemann,
Jean Mosser,
Paul Adams,
Jean-Yves Le Gall,
Véronique David
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ABSTRACT: Most features of C282Y-linked haemochromatosis support the implementation of population screening of the disorder in Caucasians. However, the penetrance of C282Y homozygosity is poorly documented and the strategy for population screening remains debated. Nine thousand three hundred and ninety-six subjects (3367 men, aged 25-40 years, and 6029 women, aged 35-50 years), attending three Health Appraisal Centres, were genotyped and assessed with respect to clinical and biochemical signs of haemochromatosis. Discriminant, logistic regression and graphic analysis were used to predict homozygosity. Results were validated in 135 homozygotes detected through other family and population studies. Fifty-four subjects (10 men and 44 women) were homozygous for C282Y. All men had abnormal iron status and most had mild clinical symptoms compatible with haemochromatosis. Identification of all homozygous men required a transferrin saturation (TS) threshold of 50% in the study group (90% specificity) and of 40% in the validation group. Homozygous women differed clinically from non-homozygotes for the presence of distal arthralgias only (18%vs 6%, P < 0.03). Thirteen (29%) were iron-deficient (serum ferritin < 13 micro g/l) and undetectable by biochemical tests. Although the population studied was not fully representative of the general population, our data strongly suggests that, in young men, large-scale screening for C282Y homozygosity is justified and can be achieved by using TS prescreening. However, in premenopausal women, large-scale screening remains to be justified with respect to the natural history of haemochromatosis and should be directly genotypic.
British Journal of Haematology 09/2002; 118(4):1170-8. · 4.94 Impact Factor
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Yves Deugnier,
Anne-Marie Jouanolle,
Jacques Chaperon,
Romain Moirand,
Catherine Pithois,
Jean-François Meyer, Michel Pouchard,
Bernard Lafraise,
Alain Brigand,
Céline Caserio-Schoenemann,
Jean Mosser,
Paul Adams,
Jean-Yves Le Gall,
Véronique David
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ABSTRACT: Most features of C282Y-linked haemochromatosis support the implementation of population screening of the disorder in Caucasians. However, the penetrance of C282Y homozygosity is poorly documented and the strategy for population screening remains debated. Nine thousand three hundred and ninety-six subjects (3367 men, aged 25–40 years, and 6029 women, aged 35–50 years), attending three Health Appraisal Centres, were genotyped and assessed with respect to clinical and biochemical signs of haemochromatosis. Discriminant, logistic regression and graphic analysis were used to predict homozygosity. Results were validated in 135 homozygotes detected through other family and population studies. Fifty-four subjects (10 men and 44 women) were homozygous for C282Y. All men had abnormal iron status and most had mild clinical symptoms compatible with haemochromatosis. Identification of all homozygous men required a transferrin saturation (TS) threshold of 50% in the study group (90% specificity) and of 40% in the validation group. Homozygous women differed clinically from non-homozygotes for the presence of distal arthralgias only (18%vs 6%, P < 0·03). Thirteen (29%) were iron-deficient (serum ferritin < 13 µg/l) and undetectable by biochemical tests. Although the population studied was not fully representative of the general population, our data strongly suggests that, in young men, large-scale screening for C282Y homozygosity is justified and can be achieved by using TS prescreening. However, in premenopausal women, large-scale screening remains to be justified with respect to the natural history of haemochromatosis and should be directly genotypic.
British Journal of Haematology 08/2002; 118(4):1170 - 1178. · 4.94 Impact Factor
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ABSTRACT: A body of evidence suggests that ceruloplasmin (Cp), the major serum copper-containing protein, acts in iron metabolism due to its ferroxidase activity which appears essential for iron movements and exchanges.
The present study investigated the serum levels of Cp and its ferroxidase activity in 53 C282Y homozygote genetic hemochromatosis (38 iron overloaded, 15 iron depleted) patients as compared to age and sex-matched healthy volunteers.
Serum levels of Cp were significantly decreased in iron-overloaded male hemochromatotic patients vs. the control group (P=0.02). Furthermore, serum ferroxidase activity was strongly and significantly lower in iron-overloaded male hemochromatotic patients (P<0.001). In contrast, in iron-depleted male hemochromatotic patients, who were under maintenance therapy by regular phlebotomies, serum levels of Cp and ferroxidase activity were not statistically different from those observed in controls.
These data: (i) show that serum Cp and ferroxidase activity are decreased when C282Y homozygote men are iron overloaded and normal when iron depleted; (ii) suggest that iron may modulate the Cp gene expression; and (iii) raise the issue of the putative role of decreased serum ferroxidase activity in the phenotypic expression of HFE-1 hereditary hemochromatosis.
Journal of Hepatology 01/2002; 36(1):60-5. · 9.26 Impact Factor
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Marie-Laure Anne,
Caroline Le Lan,
Valérie Monbet,
Catherine Boussard-Plédel,
Martine Ropert,
Olivier Sire, Michel Pouchard,
Christine Jard,
Jacques Lucas,
Jean Luc Adam,
Pierre Brissot,
Bruno Bureau,
Olivier Loréal
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ABSTRACT: Fiber evanescent wave spectroscopy (FEWS) explores the mid-infrared domain, providing information on functional chemical groups represented in the sample. Our goal is to evaluate whether spectral fingerprints obtained by FEWS might orientate clinical diagnosis. Serum samples from normal volunteers and from four groups of patients with metabolic abnormalities are analyzed by FEWS. These groups consist of iron overloaded genetic hemochromatosis (GH), iron depleted GH, cirrhosis, and dysmetabolic hepatosiderosis (DYSH). A partial least squares (PLS) logistic method is used in a training group to create a classification algorithm, thereafter applied to a test group. Patients with cirrhosis or DYSH, two groups exhibiting important metabolic disturbances, are clearly discriminated from control groups with AUROC values of 0.94+/-0.05 and 0.90+/-0.06, and sensibility/specificity of 8684% and 8787%, respectively. When pooling all groups, the PLS method contributes to discriminate controls, cirrhotic, and dysmetabolic patients. Our data demonstrate that metabolic profiling using infrared FEWS is a possible way to investigate metabolic alterations in patients.
Journal of Biomedical Optics 14(5):054033. · 3.16 Impact Factor
