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Victor R. Gordeuk - One of the best experts on this subject based on the ideXlab platform.
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African Iron Overload and hepatocellular carcinoma (HA‐7–0–080)
European journal of haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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African Iron Overload and hepatocellular carcinoma ha 7 0 080
European Journal of Haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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The Effect of the Host's Iron Status on Tuberculosis
The Journal of infectious diseases, 2007Co-Authors: Johan R. Boelaert, Stefaan J. Vandecasteele, Rui Appelberg, Victor R. GordeukAbstract:Several lines of evidence have suggested that Iron is critical for Mycobacterium tuberculosis growth in macrophages. Macrophage Iron loading in patients with African Iron Overload increases the risk of tuberculosis (TB) and may worsen TB outcome. Likewise, macrophage Iron loading may contribute to an increased predisposition toward TB in HIV infection. Human genetic disorders or variations may increase the risk of TB or worsen its outcome through macrophage Iron loading, including the haptoglobin 2-2 phenotype, NRAMP1 polymorphisms (at least in Africans and Asians), and possibly ferroportin 1 mutations, but not HFE hemochromatosis. Thus, the host's Iron status may be an important yet underevaluated factor in TB prevention and therapy and in TB vaccine design.
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Ferroportin (Q248H) mutations in African families with dietary Iron Overload.
Journal of gastroenterology and hepatology, 2005Co-Authors: Lynne Mcnamara, Victor R. Gordeuk, A. Patrick MacphailAbstract:Background: Dietary Iron Overload found in sub-Saharan Africa might be caused by an interaction between dietary Iron and an Iron-loading gene. Caucasian people with ferroportin gene mutations have Iron Overload histologically similar to that found in African patients with Iron Overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary Iron Overload, mean cell volume (MCV) and C-reactive protein (CRP) were examined in 19 southern African families. Methods: Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Statistical analysis was carried out to correlate the presence of the mutation with markers of Iron Overload and inflammation. Results: We identified three (1.4%) Q248H homozygotes and 53 (24.1%) heterozygotes in the families examined in the present study. There was no increased prevalence of the mutation in index subjects or their families. Logistic regression showed significantly higher serum ferritin concentrations with the mutation. The mean cell volume (MCV) was significantly lower, and the serum CRP significantly higher in subjects who carried the mutation. Conclusions: The present study of 19 families with African Iron Overload failed to show evidence that the ferroportin (Q248H) mutation is responsible for the condition. Logistic regression, correcting for factors influencing Iron status, did show increased ferritin levels in individuals with the mutation. The strong association with low MCV suggests the possibility that the ferroportin (Q248H) mutation might interfere with Iron supply, whereas the elevated serum CRP might indicate that the ferroportin mutation influences the inflammatory response in African populations. © 2005 Blackwell Publishing Asia Pty Ltd
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Basal endocrine status in African dietary Iron Overload
Endocrine, 2003Co-Authors: Lynette Mcnamara, Victor R. Gordeuk, Vanessa R. Panz, Frederick J. Raal, Janice Paiker, Barry I. Joffe, A. Patrick MacphailAbstract:Endocrine disturbances, notably diabetes, have been well described as a complication of Iron Overload due to hereditary hemochromatosis and β-thalassemia. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has also been well documented. The pattern of Iron loading in African Iron Overload with saturated transferrin is similar to that seen in hereditary hemochromatosis. In addition, many symptoms ascribed to pituitary dysfunction are common to both conditions. The present study was undertaken to assess whether a similar pattern of endocrine dysfunction occurs in African Iron Overload. Thirty subjects with African Iron Overload and transferrin saturation >50%, plus 30 age and sex matched normal controls were studied. An Iron profile, fasting plasma glucose, cortisol, DHEA-S, LH, FSH, growth hormone, prolactin, TSH, and FT4 levels were measured in all 60 subjects as well as testosterone in the males and estradiol in the females. Iron loading in the subjects with increased transferrin saturation ranged from moderate to severe. No significant differences were found in the mean testosterone, estradiol, LH, DHEA-S, growth hormone, prolactin, or TSH levels between the subjects and normal controls. In female subjects, although within the normal range, the mean FSH level was significantly higher, probably due to their being somewhat older and in a more advanced stage of menopause than the control females. Mean cortisol concentrations were increased in both genders in the patient group, significantly so in the females; however, values were within the reference range. We conclude therefore that there appears to be no major impairment of endocrine function in the basal state in African Iron Overload subjects with moderate to severe degrees of Iron loading.
I. T. Gangaidzo - One of the best experts on this subject based on the ideXlab platform.
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African Iron Overload and hepatocellular carcinoma (HA‐7–0–080)
European journal of haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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African Iron Overload and hepatocellular carcinoma ha 7 0 080
European Journal of Haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of Iron Overload.
European journal of haematology, 2001Co-Authors: Graça Porto, I. T. Gangaidzo, Victor R. Gordeuk, Carla Cardoso, Eugénia Cruz, José Fraga, Jorge Areias, José Carlos Oliveira, Fernanda Bravo, A. P. MacphailAbstract:To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to Iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, total lymphocyte counts and Iron status were also examined in 20 index patients with African dietary Iron Overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher Iron stores than in those without cirrhosis and with lower Iron burdens [(1.65 +/- 0.43) x 10(6)/mL vs. (2.27 +/- 0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with Iron Overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body Iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with Iron Overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African Iron Overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree of Iron loading in HFE haemochromatosis but not in African Iron Overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.
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Transferrin Polymorphism Influences Iron Status in Blacks
Clinical chemistry, 2000Co-Authors: Ishmael Kasvosve, I. T. Gangaidzo, Z. A R Gomo, Victor Moyo, Hlosukwazi Khumalo, Thokozile Saungweme, Joris R. Delanghe, Birgitte Wuyts, Elisha Mvundura, Johan R. BoelaertAbstract:Background: Genetic variants of human transferrin (TF) have been described, but little is known about their functional differences. We studied Iron status according to TF phenotype in a healthy Zimbabwean population and in subjects at risk of African Iron Overload. Methods: The study population consisted of 483 nondrinkers, 31 drinking spouse pairs, and 5 family pedigrees (n = 88) with index cases of Iron Overload. TF phenotypes were determined using starch gel electrophoresis. To evaluate Iron status, serum Iron, total Iron-binding capacity (TIBC), ferritin, and soluble TF receptors were measured, and the percentage of saturation and the serum Iron:TF ratio were calculated. The binding of the TF variants was studied by equilibrium dialysis. Results: The reference population was characterized by a high TF D allele frequency (0.050) and a complete absence of homozygous TF DD individuals. Similar allele frequencies were observed in subjects at risk of African Iron Overload. In the reference population, male TF CD heterozygotes had significantly lower ( P
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African Iron Overload
Acta clinica Belgica, 2000Co-Authors: I. Kasvosve, I. T. Gangaidzo, Z. A R Gomo, Victor R. GordeukAbstract:African Iron Overload has been recognised in sub-Saharan Africa for seventy years. The condition is distinct from the well-characterised HLA-linked haemochromatosis described in Caucasians. Increas...
Victor Moyo - One of the best experts on this subject based on the ideXlab platform.
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African Iron Overload and hepatocellular carcinoma (HA‐7–0–080)
European journal of haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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African Iron Overload and hepatocellular carcinoma ha 7 0 080
European Journal of Haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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Transferrin Polymorphism Influences Iron Status in Blacks
Clinical chemistry, 2000Co-Authors: Ishmael Kasvosve, I. T. Gangaidzo, Z. A R Gomo, Victor Moyo, Hlosukwazi Khumalo, Thokozile Saungweme, Joris R. Delanghe, Birgitte Wuyts, Elisha Mvundura, Johan R. BoelaertAbstract:Background: Genetic variants of human transferrin (TF) have been described, but little is known about their functional differences. We studied Iron status according to TF phenotype in a healthy Zimbabwean population and in subjects at risk of African Iron Overload. Methods: The study population consisted of 483 nondrinkers, 31 drinking spouse pairs, and 5 family pedigrees (n = 88) with index cases of Iron Overload. TF phenotypes were determined using starch gel electrophoresis. To evaluate Iron status, serum Iron, total Iron-binding capacity (TIBC), ferritin, and soluble TF receptors were measured, and the percentage of saturation and the serum Iron:TF ratio were calculated. The binding of the TF variants was studied by equilibrium dialysis. Results: The reference population was characterized by a high TF D allele frequency (0.050) and a complete absence of homozygous TF DD individuals. Similar allele frequencies were observed in subjects at risk of African Iron Overload. In the reference population, male TF CD heterozygotes had significantly lower ( P
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Evidence of genetic transmission in African Iron Overload.
Blood, 1998Co-Authors: Victor Moyo, I. T. Gangaidzo, Z. A R Gomo, Sandra J. Hasstedt, Hlosukwazi Khumalo, Eberhard Mandishona, Thokozile Saungweme, C. F. Kiire, A.c. Paterson, Peter BloomAbstract:Iron Overload in Africa was previously regarded as purely due to excessive Iron in traditional beer, but we recently found evidence that transferrin saturation and unsaturated Iron binding capacity may be influenced by an interaction between dietary Iron content and a gene distinct from any HLA-linked locus. To determine if serum ferritin follows a genetic pattern and to confirm our previous observations, we studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was characterized with repeated morning measurements of serum ferritin, transferrin saturation, and unsaturated Iron binding capacity after supplementation with vitamin C. For each measure of Iron status, segregation analysis was consistent with an interaction between a postulated Iron-loading gene and dietary Iron content ( P
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evidence of genetic transmission in African Iron Overload
Blood, 1998Co-Authors: Victor Moyo, I. T. Gangaidzo, Z. A R Gomo, Sandra J. Hasstedt, Hlosukwazi Khumalo, Eberhard Mandishona, Thokozile Saungweme, C. F. Kiire, A.c. Paterson, Peter BloomAbstract:Iron Overload in Africa was previously regarded as purely due to excessive Iron in traditional beer, but we recently found evidence that transferrin saturation and unsaturated Iron binding capacity may be influenced by an interaction between dietary Iron content and a gene distinct from any HLA-linked locus. To determine if serum ferritin follows a genetic pattern and to confirm our previous observations, we studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was characterized with repeated morning measurements of serum ferritin, transferrin saturation, and unsaturated Iron binding capacity after supplementation with vitamin C. For each measure of Iron status, segregation analysis was consistent with an interaction between a postulated Iron-loading gene and dietary Iron content ( P < .01). In the most likely model, transferrin saturation is 75% and serum ferritin is 985 μg/L in a 40-year-old male heterozygote with an estimated beer consumption of 10,000 L, whereas the saturation is 36% and serum ferritin is 233 μg/L in an unaffected individual with identical age, sex, and beer consumption. This segregation analysis provides further evidence for a genetic influence on Iron Overload in Africans.
Tracey A. Rouault - One of the best experts on this subject based on the ideXlab platform.
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African Iron Overload and hepatocellular carcinoma ha 7 0 080
European Journal of Haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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African Iron Overload and hepatocellular carcinoma (HA‐7–0–080)
European journal of haematology, 2009Co-Authors: Victor Moyo, I. T. Gangaidzo, Victor R. Gordeuk, Tracey A. Rouault, Rudo Makunike, Christine E. Mclaren, Hlosukwazi Khumalo, Thoko Saungweme, Clement F. KiireAbstract:Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.
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Is there a link between African Iron Overload and the described mutations of the hereditary haemochromatosis gene
British journal of haematology, 1998Co-Authors: Lynne Mcnamara, Victor R. Gordeuk, A. P. Macphail, Sandra J. Hasstedt, Tracey A. RouaultAbstract:Over 80% of Caucasian patients with hereditary haemochromatosis are homozygotes for a C282Y mutation in the HFE gene on chromosome 6. Recent evidence suggests that a genetic factor may also be involved in the pathogenesis of African Iron Overload, although the locus has not been described. PCR analysis of DNA from 25 southern Africans, identified by segregation analysis as having a high probability of carrying the putative African Iron-loading gene, failed to identify any subjects with the C282Y mutation. The possible genetic defect in African Iron Overload appears to be different from that described in most cases of hereditary haemochromatosis in Caucasians.
A. P. Macphail - One of the best experts on this subject based on the ideXlab platform.
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Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of Iron Overload.
European journal of haematology, 2001Co-Authors: Graça Porto, I. T. Gangaidzo, Victor R. Gordeuk, Carla Cardoso, Eugénia Cruz, José Fraga, Jorge Areias, José Carlos Oliveira, Fernanda Bravo, A. P. MacphailAbstract:To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to Iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, total lymphocyte counts and Iron status were also examined in 20 index patients with African dietary Iron Overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher Iron stores than in those without cirrhosis and with lower Iron burdens [(1.65 +/- 0.43) x 10(6)/mL vs. (2.27 +/- 0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with Iron Overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body Iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with Iron Overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African Iron Overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree of Iron loading in HFE haemochromatosis but not in African Iron Overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.
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Measurements of Iron status and survival in African Iron Overload.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 1999Co-Authors: A. P. Macphail, Eberhard MandishonaAbstract:INTRODUCTION Dietary Iron Overload is common in southern Africa and there is a misconception that the condition is benign. Early descriptions of the condition relied on autopsy studies, and the use of indirect measurements of Iron status to diagnose this form of Iron Overload has not been clarified. METHODS The study involved 22 black subjects found to have Iron Overload on liver biopsy. Fourteen subjects presented to hospital with liver disease and were found to have Iron Overload on percutaneous liver biopsy. Eight subjects, drawn from a family study, underwent liver biopsy because of elevated serum ferritin concentrations suggestive of Iron Overload. Indirect measurements of Iron status (transferrin saturation, serum ferritin) were performed on all subjects. Histological Iron grade and hepatic Iron concentration were used as direct measures of Iron status. RESULTS There were no significant differences in either direct or indirect measurements of Iron status between the two groups. In 75% of these subjects the hepatic Iron concentration was greater than 350 micrograms/g dry weight, an extreme elevation associated with a high risk of fibrosis and cirrhosis. Serum ferritin was elevated in all subjects and the transferrin saturation was greater than 60% in 93% of the subjects. Hepatomegaly was present in 20 of the 22 cases and there was only a moderate derangement in liver enzymes except for a tenfold increase in the median gamma-glutamyl transpeptidase concentration. There was a strong correlation between serum ferritin and hepatic Iron concentrations (r = 0.71, P = 0.006). After a median follow-up of 19 months, 6 (26%) of the subjects had died. The risk of mortality correlated significantly with both the hepatic Iron concentration and the serum ferritin concentration. CONCLUSIONS Indirect measurements of Iron status (serum ferritin concentration and transferrin saturation) are useful in the diagnosis of African dietary Iron Overload. When dietary Iron Overload becomes symptomatic it has a high mortality. Measures to prevent and treat this condition are needed.
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Is there a link between African Iron Overload and the described mutations of the hereditary haemochromatosis gene
British journal of haematology, 1998Co-Authors: Lynne Mcnamara, Victor R. Gordeuk, A. P. Macphail, Sandra J. Hasstedt, Tracey A. RouaultAbstract:Over 80% of Caucasian patients with hereditary haemochromatosis are homozygotes for a C282Y mutation in the HFE gene on chromosome 6. Recent evidence suggests that a genetic factor may also be involved in the pathogenesis of African Iron Overload, although the locus has not been described. PCR analysis of DNA from 25 southern Africans, identified by segregation analysis as having a high probability of carrying the putative African Iron-loading gene, failed to identify any subjects with the C282Y mutation. The possible genetic defect in African Iron Overload appears to be different from that described in most cases of hereditary haemochromatosis in Caucasians.