Effect Of Glucose-6-phosphate Dehydrogenase Deficiency Research Articles

Effect of combined G6PD deficiency and diabetes on protein oxidation and lipid peroxidation

BackgroundOxidative Stress, an imbalance in the pro-oxidant/antioxidant homeostasis, occurs in many physiological and non-physiological processes and several human diseases, including diabetes mellitus (DM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Since the incidence of G6PD deficiency in Jordan and many parts of the world is high, this study aimed to measure the effect of G6PD deficiency on the oxidative markers and the antioxidant glutathione (GSH) in diabetic and non-diabetic individuals.MethodsWhole blood G6PD deficiency was screened by the fluorescent spot method, and erythrocyte G6PD activity was determined using a quantitative assay. Since protein carbonyl (PC) and malondialdehyde (MDA) are the most widely measured markers for protein and lipid oxidation, respectively, plasma PC and MDA, in addition to blood GSH were determined by spectrophotometric assays, as biomarkers of oxidative stress.ResultsThe incidence of G6PD deficiency among the diabetic subjects was 15%. PC level in patients with diabetes and in G6PD-deficient subjects was 5.5 to 6-fold higher than in non-diabetic subjects with sufficient G6PD levels (p<0.001). This fold increase was doubled in diabetic patients with G6PD deficiency (p<0.001). Furthermore, the MDA level was significantly increased by 28-41% in G6PD-deficient, diabetics with sufficient G6PD, and diabetics with G6PD deficiency compared to MDA level in non-diabetic with sufficient G6PD. On the other hand, GSH was significantly reduced to half in G6PD-deficient subjects and in diabetics with G6PD-deficiency.ConclusionsThe results showed that diabetes and G6PD deficiency increased protein oxidation and lipid peroxidation. However, the combination of both disorders has an additive effect only on protein oxidation. On the other hand, GSH level is only reduced in G6PD deficiency. In addition, diabetes and G6PD deficiency appear to be genetically linked since the incidence of G6PD deficiency among people with diabetes is more than the general population.

Glucose-6-phosphate dehydrogenase deficiency reduces susceptibility to cancer of endodermal origin

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzyme defect worldwide. There is a growing scientific evidence for a protective role of G6PD deficiency against carcinogenesis. In this retrospective analysis, we tested the hypothesis that G6PD deficiency may reduce the risk of developing cancer in a tissue-specific manner.Material and methods: The study was conducted using data from 11,708 subjects undergoing gastrointestinal endoscopic procedures between 2002 and 2018 and tested for G6PD status in a teaching hospital of Northern Sardinia, Italy.Results: A 40% reduction of risk for cancer of endodermal origin was observed among G6PD-deficient patients compared with subjects with normal enzyme activity (relative risk (RR) 0.61, 95% confidence interval (CI) 0.47–0.80) in both genders, confirmed by multivariable generalized linear regression after adjusting for age, sex, smoking habits, body mass index, diabetes and socio-economic status. The ‘protective’ effect of G6PD deficiency was larger for gastric cancer (RR 0.41, 95% CI 0.18–0.99), hepatocellular carcinoma (RR 0.48, 95% CI 0.26–0.92) and colorectal cancer (RR 0.72, 95% CI 0.53–0.98), while a non-significant risk was observed for breast, prostate, lung, hematopoietic and metastases (primary site unknown).Conclusions: Our results suggest a reduced susceptibility to develop cancers, mostly of endodermal origin (stomach, colon and liver), but not of ectodermal/mesodermal origin, in carriers of G6PD deficiency. The effects of G6PD deficiency on carcinogenesis need further studies to better understand how cancer cells originating from different germ layers use pentose phosphate pathway to proliferate.

Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria.

Case fatality rates in severe falciparum malaria depend on the pattern and degree of vital organ dysfunction. Recent large-scale case-control analyses of pooled severe malaria data reported that glucose-6-phosphate dehydrogenase deficiency (G6PDd) was protective against cerebral malaria but increased the risk of severe malarial anaemia. A novel formulation of the balancing selection hypothesis was proposed as an explanation for these findings, whereby the selective advantage is driven by the competing risks of death from cerebral malaria and death from severe malarial anaemia. We re-analysed these claims using causal diagrams and showed that they are subject to collider bias. A simulation based sensitivity analysis, varying the strength of the known effect of G6PDd on anaemia, showed that this bias is sufficient to explain all of the observed association. Future genetic epidemiology studies in severe malaria would benefit from the use of causal reasoning.

Glucose-6-Phosphate Dehydrogenase Deficiency and Physical and Mental Health until Adolescence.

BackgroundTo examine the association of glucose-6-phosphate dehydrogenase (G6PD) deficiency with adolescent physical and mental health, as effects of G6PD deficiency on health are rarely reported.MethodsIn a population-representative Chinese birth cohort: “Children of 1997” (n = 8,327), we estimated the adjusted associations of G6PD deficiency with growth using generalized estimating equations, with pubertal onset using interval censored regression, with hospitalization using Cox proportional hazards regression and with size, blood pressure, pubertal maturation and mental health using linear regression with multiple imputation and inverse probability weighting.ResultsAmong 5,520 screened adolescents (66% follow-up), 4.8% boys and 0.5% girls had G6PD deficiency. G6PD-deficiency was not associated with birth weight-for-gestational age or length/height gain into adolescence, but was associated with lower childhood body mass index (BMI) gain (-0.38 z-score, 95% confidence interval (CI) -0.57, -0.20), adjusted for sex and parental education, and later onset of pubic hair development (time ratio = 1.029, 95% CI 1.007, 1.050). G6PD deficiency was not associated with blood pressure, height, BMI or mental health in adolescence, nor with serious infectious morbidity until adolescence.ConclusionsG6PD deficient adolescents had broadly similar physical and mental health indicators, but transiently lower BMI gain and later pubic hair development, whose long-term implications warrant investigation.

Some clinical and haematological effects of G6PD deficiency among individuals with sickle cell disorders in Kumasi, Ghana

Background: As to whether the presence of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency ameliorates or worsens sickle cell disease (SCD) is still not clear. Aim and Objectives: This study was therefore aimed at investigating whether the presence of G6PD deficiency among SCD subjects (HbSS and HbSC) would have any significant impact on the severity of crisis and haematological indices. Subjects and Methods: A structured questionnaire was used to obtain information on the clinical state of the subjects. The qualitative methaemoglobin reduction method was used to screen for G6PD deficiency, followed by the measurement of some haematological indices. Results: The data showed that the different genotypes of SCD subjects had similar clinical features, voiding of darkened urine, frequency of crises and blood transfusion, p &gt; 0.05. Statistically, the presence of G6PD-deficency among the HbSS and HbSC patients had no significant impact on their haematological indices (p &gt; 0.05), except the glutathione stability, (p &lt; 0.05). However, a statistically significant difference occurred between the haematological indices of the SS and SC patients (p &lt; 0.05), with improved values in the SC subjects. The presence of the G6PD in the SCD population was quite low (6.49%) compared with other similar studies (8 - 30 %) among the general population. These findings strongly support some reports that SCD subjects with G6PD-deficiency do not show a compromised function due to the combined defects.

Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates

Background: The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to be damaged by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus.Objective: This study was carried out to detect erythrocyte G6PD deficiency in neonatal hyperbilirubinemia.Methods and design: To determine the frequency and effect of G6PD deficiency, this study was conducted on 202 neonates with indirect hyperbilirubinemia. All term and preterm babies up to 13 day of age admitted with clinically evident jaundice were taken for the study. G6PD activity is measured by the UV-Kinetic Method using cellular enzyme determination reagents by spectrophotometry according to manufacturer’s instructions.Results: A total of 202 babies were enrolled in this study. Male babies outnumbered the female (71.3% versus 28.7%). Mean age of the study newborns was 3.75 ± 2.5 days. Eighteen neonates (8.9%) had G6PD deficiency, all are males. One case had combined G6PD deficiency and RH incompatibility. Mean serum total bilirubin was 17.2 ± 4.4 in G6PD deficient cases. There was significant positive correlation between the time of appearance of jaundice in days and G6PD levels in G6PD deficient cases.Conclusion: Neonatal hyperbilirubinemia is associated with various clinical comorbidities. G6PD deficiency is found to one important cause of neonatal jaundice developing on day 2 onwards.

Common G6PD Variant from Saudi Population and its Prevalence

Biochemical characterization of erythrocyte glucose-6-phosphate-dehydrogenase from 18 unrelated deficient Saudi Subjects from Al-Hassa and Al-Qatif areas of the Eastern Province was carried out according to WHO procedures. This had led to the identification of one genetically determined common variant, "G6PD Mediterranean". The overall prevalence rate of this deficiency in these areas was determined to be in excess of 42%. None of the subjects studied displayed any sign of favism, a condition usually associated with G6PD Mediterranean, which is characterized by a very low intracellular enzyme activity.

Glucose-6-phosphate dehydrogenase deficiency severely restricts the biotransformation of daunorubicin in human erythrocytes

Recognition and analysis of distinct mechanisms by which primaquine and other hemolytic drugs activate the hexose monophosphate shunt (HMS) have suggested a hitherto unsuspected pharmacogenetic interaction between daunorubicin metabolism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Because this deficiency is very common, and because anthracyclines are indispensable antitumor antibiotics that are biotransformed mainly by carbonyl reductase, we have compared the reductase-mediated conversion of daunorubicin to daunorubicinol and the conversion of doxorubicin to doxorubicinol in G6PD-deficient and nondeficient erythrocytes. We found that even without G6PD deficiency, the HMS dehydrogenases selectively limited daunorubicin metabolism, as contrasted with that of doxorubicin. The milder GdA − variety of G6PD deficiency restricted the biotransformation of daunorubicin at therapeutic levels, in hemolysates and intact erythrocytes, within 15 minutes, for at least 24 hours. The bioconversion defect was even more severe in Gd Mediterranean G6PD deficiency. Primaquine aldehyde competed with daunorubicin as a substrate for carbonyl reductase. These studies show that HMS dehydrogenase activity controls carbonyl reductase-dependent biotransformation. New issues arise concerning possible effects of G6PD deficiency on the oncolytic and toxic properties of anthracyclines that are effective substrates for carbonyl reductase and also on nonxenobiotic reactions catalyzed by this enzyme.