RESUMEN

BACKGROUND AND OBJECTIVES: To investigate the prevalence, genotype and haematological characteristics of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the blood donor population of Wuxi area (Jiangsu Province, China) and to assess the impact of their red blood cell (RBC) units on clinical transfusion. MATERIALS AND METHODS: We conducted genotyping and large-scale screening for G6PD enzyme activity in the blood donors of Wuxi City. In addition, we assessed the haematological parameters of G6PD-deficient and non-deficient blood donors, and investigated the adverse transfusion reactions in patients transfused with G6PD-deficient blood. RESULTS: We investigated 17,113 blood donors, among whom 44 (0.26%) were tested positive for G6PD deficiency. We identified 40 G6PD gene variants, among which c.1388G>A, c.1376G>T, c.1024C>T and c.95A>G were common. In addition, we identified two novel G6PD gene variants, c.1312G>A and c.1316G>A. The G6PD-deficient and non-deficient blood samples showed a significant difference in the RBC, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), RBC distribution width, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) values. However, the two samples showed no significant difference in the haemolysis rate at the end of the storage period. Finally, transfusion with G6PD-deficient RBC units did not lead to any adverse transfusion reactions. CONCLUSION: The positive rate of G6PD deficiency in the blood donor population of Wuxi City is 0.26%, and the genetic variants identified in this population are consistent with the common genetic variants observed in the Chinese population. Blood centres can establish a database on G6PD-deficient blood donors and mark their RBC units to avoid their use for special clinical patients.

Asunto(s)

Anemia Hemolítica , COVID-19 , Deficiencia de Glucosafosfato Deshidrogenasa , Niño , Humanos , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etiología , COVID-19/complicaciones , Glucosafosfato Deshidrogenasa , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , SARS-CoV-2

RESUMEN

Background Glucose-6-phosphate dehydrogenase deficiency, known as G6PD deficiency, is a common hematological disease in the Eastern Province. The presence of Glucose-6-phosphate dehydrogenase enzyme in the erythrocyte is crucial, as it aids in the protection of RBCs by preventing cellular damage. It was found that more than 400 million people in the world lack this enzyme, making it the most common enzyme deficiency worldwide. Because of the high prevalence of the disease in the world and the paucity of research in Saudi Arabia about G6PD deficiency, the idea of examining and assessing the awareness and knowledge of parents who have children affected with G6PD emerged. Objective This study aimed to evaluate parental knowledge regarding G6PD deficiency, identify the common and spread misconceptions regarding the disease, provide general insight for physicians about parental knowledge, and propose strategies to educate parents about G6PD deficiency. Methods This cross-sectional study was conducted from September 2022 to May 2023 on 459 individuals from the Eastern Province, Saudi Arabia. Using a questionnaire, parents with variable education levels and incomes participated. The questionnaire was available in both Arabic and English. The study aimed to gather comprehensive data regarding parental awareness and knowledge of G6PD deficiency, it focused on evaluating levels of awareness, knowledge, and misinformation of the participants. Data were analyzed by using Statistical Package for the Social Sciences, ver 22 (IBM Corp., Armonk, NY). The chi-square test was applied to check any association between demographics and level of knowledge (Good and Poor). Multiple logistic regression analysis was performed on significant demographic variables and an odds ratio with a 95% confidence interval was calculated. P < 0.05 was considered statistically significant. Results The study included a total of 459 participants, 309 (67.3%) were females and 150 (32.7%) were males. Regarding the demographics, the majority of the participants were <40 years old (61.9%), Saudi (99.3%), married (98.5%), having bachelor's/diploma level or above (Master/PhD) (76.9%), having inherited disorder (44.2%), and having a family history of chronic diseases (82.6%). Furthermore, regarding the knowledge of the disease, the majority of the participants who recognized the disease (82.1%) were familiar with the term fava bean anemia rather than it being called G6PD deficiency anemia. On the other hand, 73.2% of the participants were unable to recognize the disease and had never heard of G6PD deficiency anemia. In addition, the majority of participants had deficient information regarding medication triggers (61.4%), whether the gender of a person is linked to G6PD (77.5%), and whether both parents must be carriers to have a child with G6PD deficiency anemia (50.9%). Female respondents proved to be more knowledgeable regarding this topic as 57.9% of them showed good knowledge as compared to (44.7%) of the male subjects. Conclusion There are discrepancies in the level of awareness among research participants. Our result indicates the need for educational interventions regarding the nomenclature, medication triggers, inheritance mode and its relation to gender, and the symptoms of the disease and its severity. Therefore, it is advised to spread awareness in the eastern province through brochures, medical campaigns, and by healthcare professionals in different medical organizations.

RESUMEN

Introduction Glucose-6-phosphate dehydrogenase deficiency (G6PD) is recognized as the most common enzyme disorder globally, impacting over 400 million individuals. The disease is highly prevalent in Saudi Arabia. This study aimed to assess parents' awareness of G6PD in Saudi Arabia and identify misconceptions for targeted educational interventions, aiming to enhance awareness and condition management. Methods A structured online questionnaire was used to gather information from July 18th, 2023, to August 1st, 2023. The survey targeted parents of Saudi children who resided in various regions across Saudi Arabia and collected a total of 531 responses. Data analysis involved descriptive statistics, chi-square tests, and probit regression. A significance level of p<0.05 was employed to interpret the results. Results A statistically significant associations were found among parents with Glucose-6-phosphate dehydrogenase deficiency-deficient children, including gender-related (odd ratio = 2.91, 99% CI: 1.986-4.301), awareness of the genetic link (odd ratio = 2.49, 99% CI: 1.701-3.639), specific medications (odd ratio =1.890, 99% CI: 1.262-2.853), loss of appetite (odd ratio= 0.629, 95% CI: 0.398-0.990), jaundice (odd ratio = 3.01, 99% CI: 1.877-4.983), increased fluid intake (odd ratio= 1.53, 95% CI: 1.091-2.139), receiving blood transfusions (odd ratio = 1.54, 95% CI: 1.101-2.157), seeking online information (odd ratio = 1.92, 99% CI: 1.250-2.940), and consulting healthcare professionals (odd ratio = 3.24, 99% CI: 2.065-5.107). Conclusion Regional disparities in glucose-6-phosphate dehydrogenase deficiency awareness among parents in Saudi Arabia are evident, with the central region demonstrating the highest level of awareness. Understanding glucose-6-phosphate dehydrogenase deficiency risk factors, medication triggers, and clinical symptoms plays a significant role in parental knowledge, emphasizing the need for region-specific education and awareness programs.

RESUMEN

BACKGROUND: Recent studies revealed the glucose-6-phosphate dehydrogenase (G-6-PD) deficiency prevalence of 7.7-10% among Thai blood donors. Transfusion of red blood cells (RBCs) from these subjects potentially causes haemolysis in recipients. METHODS: RBC units from the National Blood Centre were sampled to assess G-6-PD levels using spectrophotometry. Patients with pure underproduction anaemia requiring blood transfusion were randomised to receive G-6-PD-deficient versus normal ABO-matched RBCs. Pre- and 48-h post-transfusion indirect bilirubin, haemoglobin, haematocrit, lactate dehydrogenase (LDH) and haptoglobin were measured. RESULTS: From April 2020 to March 2021, 374 RBC units were tested for G-6-PD, and that 25 were found to be G-6-PD deficient. Twelve units of G-6-PD-deficient RBCs and 14 units of normal RBCs were given to patients who met the inclusion criteria. The median (interquartile range) increases of indirect bilirubin in G-6-PD-deficient (N = 11) versus normal RBCs (N = 13) were + 0.12 (0.27) versus + 0.01 (1.3) mg/dl, p = 0.030), respectively. The median increases of haemoglobin were 1.00 (0.50) versus + 0.80 (0.95), p = 0.910, respectively. The increases in haematocrit were 2.59 (1.9) versus 2.29 (2.1), p = 0.733, respectively. There were no significant differences in changes of LDH and haptoglobin levels and no transfusion reactions. DISCUSSION: G-6-PD-deficient packed red cells were associated with mildly elevated indirect bilirubin after transfusion, but there was no observed clinical symptoms.

Asunto(s)

Anemia , Deficiencia de Glucosafosfato Deshidrogenasa , Anemia/terapia , Bilirrubina , Transfusión de Eritrocitos , Glucosafosfato Deshidrogenasa , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Deficiencia de Glucosafosfato Deshidrogenasa/terapia , Haptoglobinas , Hemoglobinas , Humanos

RESUMEN

Methemoglobinemia (MetHb) is a rare, life-threatening condition that occurs when the body is exposed to oxidative stress. It is typically corrected through the glucose-6-phosphate dehydrogenase (G6PD)-dependent shunt. G6PD deficiency is the most common enzymatic deficiency worldwide. This genetic disorder makes patients susceptible to oxidative stress and reduces the expected life span of erythrocytes (red blood cells (RBCs)) among other cells. G6PD deficiency is asymptomatic in most cases unless exogenous stressors are introduced, whether they are dietary, iatrogenic, or infections, such as the highly transmissible serotype of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report a case of an 11-year-old male with known insulin-dependent diabetes mellitus (IDDM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, who was found to develop methemoglobinemia after being infected by the SARS-CoV-2 virus. The direct effects of COVID-19 on children were reported to be lower than on adults. However, the effects of COVID-19 on children with comorbidities, such as G6PD deficiency in our patient, are understood only to a minimal extent. Moreover, identifying cases of G6PD deficiency prior to initiating treatment with methylene blue, hydroxychloroquine (HCQ), or other contraindicated agents is essential to prevent further deterioration in symptoms.

RESUMEN

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder that may lead to transfusion-requiring acute hemolytic anemia (AHA) triggered by fava beans ingestion, infection or some drugs. The gene encoding for G6PD carries a large number of genetic variants that have varying pathogenicity. We reported on three G6PD variants in the Gaza Strip Palestinian population with differing clinical impacts and frequencies: G6PD Mediterraneanc.563T, African G6PD A-c.202A/c.376G, and G6PD Cairoc.404C. We also identified a novel G6PD missense (Ser179Asn) mutation c.536G > A "G6PD Gaza". In this work we explore the effect of these four genetic variants on the structural and substrate (NADP+ and G6P) binding characteristics of the G6PD enzyme using the Monte Carlo (MC) flexible docking and molecular dynamics (MD) simulation approaches. We report that G6PD A-c.202A/c.376G, G6PD Mediterraneanc.563T, G6PD Cairoc.404C and G6PD Gazac.536A mutations cause significant structural changes in G6PD enzyme to induce conformational instability leading to the loss of binding of one or both substrates and are causative of G6PD deficiency.

Asunto(s)

Glucosa-6-Fosfato/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/genética , NADP/metabolismo , Mutación Puntual , Glucosafosfato Deshidrogenasa/química , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Unión Proteica , Multimerización de Proteína

Asunto(s)

Infecciones por Coronavirus , Glucosafosfato Deshidrogenasa , Lesión Pulmonar , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Hemólisis , Humanos , Hidroxicloroquina , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19

RESUMEN

While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency.

Asunto(s)

Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/tratamiento farmacológico , Inhibidores Enzimáticos/efectos adversos , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Hemólisis , Hidroxicloroquina/efectos adversos , Neumonía Viral/complicaciones , Neumonía Viral/tratamiento farmacológico , Anciano , Azitromicina/uso terapéutico , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Transfusión Sanguínea , COVID-19 , Terapia de Reemplazo Renal Continuo , Quimioterapia Combinada , Inhibidores Enzimáticos/uso terapéutico , Haptoglobinas/análisis , Humanos , Hidroxicloroquina/uso terapéutico , Hipoxia/inducido químicamente , Hipoxia/complicaciones , Masculino , Nasofaringe/virología , Pandemias , Síndrome de Dificultad Respiratoria/complicaciones , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/aislamiento & purificación , SARS-CoV-2

RESUMEN

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in Western Countries. Evidence indicates that Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, a common genetic abnormality, may protect against ischemic heart and cerebrovascular disease, ocular vascular disorders, and colorectal cancer. This study was undertaken to ascertain whether G6PD deficiency may protect against AMD. Materials and Methods: 79 men with late-stage AMD and 79 male, age-matched cataract controls without AMD were recruited in March-December 2016. Smoking status, clinical history, and drug use were recorded. A blood sample was taken from each participant. Complete blood count, hemoglobin, glucose, creatinine, cholesterol, triglycerides, transaminases, bilirubin, and erythrocyte G6PD activity were measured. Stepwise logistic regression was used to investigate the association between G6PD deficiency and AMD. Results: G6PD deficiency was found in 7 (8.9%) AMD patients and 8 (10.1%) controls, a not statistically significant difference. Stepwise logistic regression disclosed that AMD was significantly associated with increased diastolic blood pressure (OR=1.09, 95% CI=1.03-1.15, P=0.02) and LDL-cholesterol (OR=1.02, 95% CI=1.0001-1.03, P=0.049) and lower values of white blood cell (WBC) count (OR=0.71, 95% CI=0.56-0.88, P=0.02) and aspartate aminotransferase (AST) (OR=0.92, 95% CI=0.85-0.99, P=0.044). Conclusion: Results suggest that G6PD deficiency has no protective effect on nor is a risk factor for AMD. Larger studies are necessary to confirm whether increased diastolic blood pressure and LDL-cholesterol and lower values of WBC count and AST are risk factors for AMD.

Asunto(s)

Catarata/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Degeneración Macular/metabolismo , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Catarata/epidemiología , Catarata/genética , Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Humanos , Italia/epidemiología , Degeneración Macular/epidemiología , Degeneración Macular/genética , Masculino , Persona de Mediana Edad , Factores de Riesgo

RESUMEN

The deficiency of glucose­6­phosphate dehydrogenase (G6PD) is one of the most common inborn errors of metabolism worldwide. This congenital disorder generally results from mutations that are spread throughout the entire gene of G6PD. Three single-point mutations for G6PD have been reported in the Mexican population and named Veracruz (Arg365His), G6PD Seattle (Asp282His), and G6PD Mexico DF (Thr65Ala), whose biochemical characterization have not yet been studied. For this reason, in this work we analyzed the putative role of the three mutations to uncover the functional consequences on G6PD activity. To this end, was developed a method to clone, overexpress, and purify recombinant human G6PD. The results obtained from all variants showed a loss of catalysis by 80 to 97% and had a decrease in affinity for both physiological substrates with respect to the wild type (WT) G6PD. Our results also showed that the three mutations affected three-dimensional structure and protein stability, suggesting an unstable structure with low conformational stability that affected its G6PD functionality. Finally, based on the biochemical characterization of the unclassified G6PD Mexico DF, we suggest that this variant could be grouped as a Class I variant, because biochemical data are similar with other Class I G6PDs.

Asunto(s)

Clonación Molecular , Genética de Población , Glucosafosfato Deshidrogenasa/química , Glucosafosfato Deshidrogenasa/genética , Mutación , Dicroismo Circular , Activación Enzimática , Estabilidad de Enzimas , Glucosafosfato Deshidrogenasa/aislamiento & purificación , Humanos , Cinética , México , Modelos Moleculares , Conformación Proteica , Proteínas Recombinantes , Relación Estructura-Actividad , Termodinámica

RESUMEN

Thalassemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency are the most common inherited blood disorders. They are distributed among populations living in malaria endemic regions resulting in survival advantage from severe malaria disease. The aims of this study were to analyze the prevalence of thalassemias and G6PD deficiency at the Ramathibodi Hospital, Bangkok, Thailand. A total of 616 adult and 174 cord blood samples were collected and analyzed for red blood cell (RBC) parameters, hemoglobin (Hb) typing and DNA analysis for G6PD mutations and α-thalassemia (α-thal). The two most prominent types of thalassemia were heterozygous Hb E (HBB: c.79G>A), (19.5% in newborns and 35.6% in adults) followed by heterozygous α-thal-2 [-α3.7 (rightward) deletion] at 18.7% in newborns and 19.5% in adults. After performing G6PD genotyping using multiplex amplification refractory mutation system-polymerase chain reaction (multiplex ARMS-PCR) for 10 G6PD mutations, the prevalence of G6PD mutation was found in 12.0% of newborns and 11.7% of adults. The G6PD Viangchan [871 (G>A)] is the most common G6PD mutation in newborns (42.9%) and adults (52.8%). In addition, coinheritance of various types of thalassemia with G6PD deficiency were found. The results indicated that heterozygous Hb E and G6PD Viangchan are predominant both in newborns and adults in this study.

Asunto(s)

Deficiencia de Glucosafosfato Deshidrogenasa , Mutación , Talasemia , Adulto , Femenino , Deficiencia de Glucosafosfato Deshidrogenasa/sangre , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Humanos , Recién Nacido , Masculino , Prevalencia , Tailandia/epidemiología , Talasemia/sangre , Talasemia/epidemiología , Talasemia/genética

RESUMEN

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. OBJECTIVES: Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. METHODS: Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. RESULTS: In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). CONCLUSION: We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.

Asunto(s)

Regiones no Traducidas 3' , Alelos , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/genética , Intrones , Polimorfismo de Nucleótido Simple , Árabes , Preescolar , Activación Enzimática , Exones , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Glucosafosfato Deshidrogenasa/metabolismo , Haplotipos , Hemólisis , Humanos , Lactante , Masculino , Mutación , Fenotipo

RESUMEN

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation with G6PD deficiency severity, we report the construction, cloning and expression as well as the detailed kinetic and stability characterization of three purified clinical variants of G6PD that present in the Mexican population: G6PD Zacatecas (Class I), Vanua-Lava (Class II) and Viangchan (Class II). For all the G6PD mutants, we obtained low purification yield and altered kinetic parameters compared with Wild Type (WT). Our results show that the mutations, regardless of the distance from the active site where they are located, affect the catalytic properties and structural parameters and that these changes could be associated with the clinical presentation of the deficiency. Specifically, the structural characterization of the G6PD Zacatecas mutant suggests that the R257L mutation have a strong effect on the global stability of G6PD favoring an unstable active site. Using computational analysis, we offer a molecular explanation of the effects of these mutations on the active site.

Asunto(s)

Indio Americano o Nativo de Alaska/genética , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/química , Glucosafosfato Deshidrogenasa/genética , Mutación , Dominio Catalítico , Clonación Molecular , Biología Computacional/métodos , Cristalografía por Rayos X , Glucosafosfato Deshidrogenasa/metabolismo , Humanos , Cinética , México , Modelos Moleculares , Estabilidad Proteica , Estructura Terciaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Aspirin is an important drug in acute coronary syndromes (ACS) and percutaneous coronary interventions (PCI). However, its use is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (risk for haemolytic anaemia). We report the management of 2 patients with class II G6PD deficiency and non-ST-segment elevation ACS (NSTE-ACS). CASE DESCRIPTION: The two patients were safely and efficiently treated with dual antiplatelet treatment (DAPT, aspirin plus ticagrelor) and PCI using new-generation drug-eluting stent (DES) despite G6PD deficiency. WHAT IS NEW AND CONCLUSION: NSTE-ACS management with DAPT and DES is probably safe and effective in class II G6PD-deficient patients.

Asunto(s)

Síndrome Coronario Agudo/terapia , Stents Liberadores de Fármacos , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Inhibidores de Agregación Plaquetaria/administración & dosificación , Síndrome Coronario Agudo/fisiopatología , Adenosina/administración & dosificación , Adenosina/efectos adversos , Adenosina/análogos & derivados , Anciano , Aspirina/administración & dosificación , Aspirina/efectos adversos , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticagrelor

RESUMEN

We describe a gold nanoparticle-based technique for the detection of single-base mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene, a condition that can lead to neonatal jaundice and hemolytic anemia. The aim of this technique is to clearly distinguish different mutations frequently described within the Asian population from their wild-type counterparts and across different mutant variants. Gold nanoparticles of different sizes were synthesized, and each was conjugated with a single-strand DNA (ssDNA) sequence specific for a particular mutation in the G6PD gene. It was found that only mutant targets presented a characteristic band on the agarose gel, indicating the successful formation of dimeric nanostructures. No such dimer bands were observed for the wild-type targets. The difference in the relative dimer band levels allowed different mutant variants to be distinguished from one another. The technique was further validated using G6PD-deficient patient samples. This simple mutation detection method with direct result readout is amenable for rapid and mass screening of samples.

Asunto(s)

ADN/análisis , Electroforesis en Gel de Agar , Glucosafosfato Deshidrogenasa/genética , Oro/química , Nanopartículas del Metal/química , ADN/metabolismo , Sondas de ADN/química , Sondas de ADN/metabolismo , ADN de Cadena Simple/síntesis química , ADN de Cadena Simple/metabolismo , Dimerización , Glucosafosfato Deshidrogenasa/metabolismo , Humanos , Hibridación de Ácido Nucleico , Tamaño de la Partícula , Mutación Puntual

RESUMEN

BACKGROUND: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Sardinia, Italy. Evidence indicates that G6PD-deficient patients are protected against vascular disease. Little is known about the relationship between G6PD deficiency and diabetes mellitus. The purpose of this study was to compare G6PD deficiency prevalence in Sardinian diabetic men with severe retinal vascular complications and in age-matched non-diabetic controls and ascertain whether G6PD deficiency may offer protection against this vascular disorder. METHODS: Erythrocyte G6PD activity was determined using a quantitative assay in 390 diabetic men with proliferative diabetic retinopathy (PDR) and 390 male non-diabetic controls, both aged ≥50 years. Conditional logistic regression models were used to investigate the association between G6PD deficiency and diabetes with severe retinal complications. RESULTS: G6PD deficiency was found in 21 (5.4 %) diabetic patients and 33 (8.5 %) controls (P=0.09). In a univariate conditional logistic regression model, G6PD deficiency showed a trend for protection against diabetes with PDR, but the odds ratio (OR) fell short of statistical significance (OR=0.6, 95% confidence interval=0.35-1.08, P=0.09). In multivariate conditional logistic regression models, including as covariates G6PD deficiency, plasma glucose, and systemic hypertension or systolic or diastolic blood pressure, G6PD deficiency showed no statistically significant protection against diabetes with PDR. CONCLUSIONS: The prevalence of G6PD deficiency in diabetic men with PDR was lower than in age-matched non-diabetic controls. G6PD deficiency showed a trend for protection against diabetes with PDR, but results were not statistically significant.

Asunto(s)

Retinopatía Diabética/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/epidemiología , Retinopatía Diabética/fisiopatología , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Deficiencia de Glucosafosfato Deshidrogenasa/fisiopatología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Agudeza Visual

RESUMEN

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is an X-linked recessive enzymopathy responsible for acute haemolysis following exposure to oxidative stress. Drugs which induce haemolysis in these patients are often used in anaesthesia and perioperative pain management. Neurosurgery and few drugs routinely used during these procedures are known to cause stress situations. Associated infection and certain foodstuffs are also responsible for oxidative stress. Here, we present two patients with G-6-PD deficiency who underwent uneventful neurosurgical procedures. The anaesthetic management in such patients should focus on avoiding the drugs implicated in haemolysis, reducing the surgical stress with adequate analgesia, and monitoring for and treating the haemolysis, should it occur.