Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with iron status in persons with type 2 diabetes mellitus

Arredondo, Miguel; Jorquera, Denisse; Carrasco, Elena; Albala, Cecilia; Hertrampf, Eva

doi:10.1093/ajcn/86.5.1347

Cited by 34 publications

(26 citation statements)

References 29 publications

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“…They showed elevated serum ferritin and TBI (Arredondo et al 2007). In this study, we found similar behavior in both T2D parents and their offspring, with elevated serum ferritin, TBI and low transferrin receptor.…”

Section: Discussionsupporting

confidence: 77%

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Type 2 diabetic patients and their offspring show altered parameters of iron status, oxidative stress and genes related to mitochondrial activity

et al. 2012

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Type 2 diabetes (T2D) is directly related to alterations in iron status, oxidative stress and decreased mitochondrial activity, but the possible interaction of these parameters among T2D patients and their offspring is unclear. The whole study included 301 subjects: 77 T2D patients and one of their offspring and 51 control subjects with one of their offspring. The offspring were older than 20 years old. We measured parameters of iron status (serum iron, ferritin and transferrin receptor), diabetes (pre and post-prandial glucose, insulin, lipids), oxidative stress (Heme oxygenase activity, TBARS, SOD, GSH, Vitamin E), as well as the expression of genes in blood leukocytes related to mitochondrial apopotosis (mitofusin and Bcl/Bax ratios). The offspring of T2D patients had increased levels of serum ferritin (P < 0.01) and lower transferrin receptor (P < 0.008); higher insulin (P < 0.03) and total and LDL cholesterol; higher heme oxygenase and SOD activities increased TBARS and lower GSH; decreased mitofusin and Bcl/Bax expression ratios compared to offspring of normal subjects. These results suggest that the offspring of T2D patients could have an increased metabolic risk of develop a cardiovascular disease mediated by oxidative stress and iron status.

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Section: Discussionsupporting

confidence: 77%

“…Bilirubin concentrations were measured at 530 nm (Shimadzu, model UV-1601). HO activity was expressed as nmole of bilirubin/mg protein/h (bilirubin molar extinction coefficient: e = 43.5 mM -1 9 cm -1 ) (Arredondo et al 2007). …”

Section: Heme Oxygenase Activitymentioning

confidence: 99%

Type 2 diabetic patients and their offspring show altered parameters of iron status, oxidative stress and genes related to mitochondrial activity

et al. 2012

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“…As described earlier, 33 the distribution of the numbers of (GT) n showed a bimodal pattern with two main peaks at 21 GT repeats (15.2% for inhibitor-positive patients and 14.3% for inhibitor-negative patients) and 29 GT repeats (24.7% for inhibitor-positive patients and 24.5% for inhibitor-negative patients). Based on the frequency distribution in our cohort of patients, and as described in previous reports, [33][34][35] we divided the alleles into three subclasses: class S (<21 repeats); class M (21-29 repeats) and class L (≥30 repeats) alleles. The c 2 test for independence between allelic classes confirmed the Hardy-Weinberg equilibrium in both the inhibitor-negative and inhibitor-positive groups.…”

Section: Allele Frequencies At the Polymorphic Locussupporting

confidence: 71%

Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

et al. 2013

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Induction of heme oxygenase-1, a stress-inducible enzyme with anti-inflammatory activity, reduces the immunogenicity of therapeutic factor VIII in experimental hemophilia A. In humans, heme oxygenase-1 expression is modulated by polymorphisms in the promoter of the heme oxygenase-1-encoding gene (HMOX1). We investigated the relationship between polymorphisms in the HMOX1 promoter and factor VIII inhibitor development in severe hemophilia A. We performed a case-control study on 99 inhibitor-positive patients and 263 patients who did not develop inhibitors within the first 150 cumulative days of exposure to therapeutic factor VIII. Direct sequencing and DNA fragment analysis were used to study (GT) n polymorphism and single nucleotide polymorphisms located at -1135 and -413 in the promoter of HMOX1. We assessed associations between the individual allele frequencies or genotypes, and inhibitor development. Our results demonstrate that inhibitor-positive patients had a higher frequency of alleles with large (GT) n repeats (L: n≥30), which are associated with lesser heme oxygenase-1 expression (odds ratio 2.31; 95% confidence interval 1. 46-3.66; P<0.001]. Six genotypes (L/L, L/M, L/S, M/M, M/S and S/S) of (GT) n repeats were identified (S: n<21; M: 21≤n<30). The genotype group including L alleles (L/L, L/M and L/S) was statistically more frequent among inhibitor-positive than inhibitor-negative patients, as compared to the other genotypes (33.3% versus 17.1%) (odds ratio 2.21, 95% confidence interval 1.30-3.76; P<0.01). To our knowledge, this is the first association identified between HMOX1 promoter polymorphism and development of anti-drug antibodies. Our study paves the way towards modulation of the endogenous anti-inflammatory machinery of hemophilia patients to reduce the risk of inhibitor development Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

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“…Free radical formation may play a role in the pathogenesis of diabetes by disrupting insulin action and total body glucose disposal. The iron act as a powerful prooxidant and the oxidative stress is increased in glucose-intolerant states [27][28][29]. The presence of poor glycemic control, hyperglycemia, iron overload, and protein glycation will all lead to oxidative stress causing the early appearance of microvascular complications (retinopathy and nephropathy) [8,24,30].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Serum-Free Iron and Glycated Hemoglobin in Uncontrolled Type-Ii Diabetic Patients

Kamalam

Ganesan

Anbazhagan

2016

Asian J Pharm Clin Res

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Objective: Diabetes mellitus (DM) is a common health problem in the world. Free iron may contribute to the pathogenesis and progress of this disease and its complication. Iron causes hyperinsulinemia by decreasing the insulin uptake and metabolism by hepatocytes. Elevated iron stores are commonly found in insulin resistance. Iron in its free form is known to induce oxidation of biomolecules by producing harmful hydroxyl radicals. In this study, we aimed to estimate and compare the serum levels of free iron in diabetes and healthy individuals.Methods: This study included 244 subjects in two groups. Group-I comprised 204 subjects with DM and Group-II comprised 40 healthy subjects. Blood sugar, free iron, and glycated hemoglobin were analyzed in blood samples using standard kits. The results of all the parameters were expressed as mean±standard deviation. Student t-test was done to assess the statistical significance between two groups. The association between the parameters was studied by Pearson correlation. Results:In this study, we found a significant increase in serum free iron in Group-I (p<0.01) when compared with Group-II. A significant correlation between the serum free iron and glycated hemoglobin (r=0.59; p<0.001) and fasting blood sugar (r=0.43; p<0.001). Conclusion:The elevated serum free iron in uncontrolled diabetes may contribute to oxidative stress which may be associated with complications of diabetes.

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Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with iron status in persons with type 2 diabetes mellitus

Abstract: Type 2 diabetes patients carrying short (GT)(n) repeats may have higher ferritin values and greater HO enzymatic activity and may have greater susceptibility to diabetes than may those with long (GT)(n) repeats.

Cited by 34 publications

References 29 publications

Type 2 diabetic patients and their offspring show altered parameters of iron status, oxidative stress and genes related to mitochondrial activity

Type 2 diabetic patients and their offspring show altered parameters of iron status, oxidative stress and genes related to mitochondrial activity

Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

Evaluation of Serum-Free Iron and Glycated Hemoglobin in Uncontrolled Type-Ii Diabetic Patients

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