Dataset Information

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

ABSTRACT:

Background

Oxidative 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.

Methods

Whole 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.

Results

The 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.

Conclusions

The 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.

SUBMITTER: Karadsheh NS

PROVIDER: S-EPMC8705147 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked inherited erythroenzymopathy in Thailand. The clinical and hematological manifestations of G6PD deficiency are variable.ObjectiveThis study aimed to characterize the genotype-phenotype correlation of G6PD mutations in Thai pediatric patients who were followed-up in Phramongkutklao Hospital, a tertiary center in central Thailand. Material and Method. A total of 102 children including 73 males (71.6%) and 29 females (28.4%) were included in our study. Mutation analysis was performed by direct DNA sequencing of all coding exons of the G6PD gene. Ninety-one patients (89.2%) were presented with neonatal hyperbilirubinemia and 11 patients (10.8%) were presented with acute hemolytic anemia beyond the neonatal period.ResultsMolecular analysis of the G6PD gene in 102 G6PD-deficient Thai children identified 12 different mutations. G6PD Viangchan (871G?>?A) and G6PD Canton (1376G?>?T) were the first (46.2%) and the second (15.4%) most common identified mutations among both male and female G6PD-deficient individuals, respectively. All affected males were hemizygous for G6PD mutations and had an average G6PD level of 16.7?±?11.5 (3-76) IU/ml.RBC. Majority of female patients (27 in 29, 93.1%) were heterozygous for G6PD mutations and had an average G6PD level of 133.6?±?43.4 (9-195) IU/ml.RBC. Two female patients (6.9%) were either homozygous or compound heterozygous for the mutations and had G6PD level in the affected male range (35 and 10 IU/ml.RBC). Only 1 in 27 heterozygous females (3.7%) had G6PD level in the affected male range (9 IU/ml.RBC) which is possibly explained by nonrandom X-chromosome inactivation. The correlation of genotypes, G6PD levels, and clinical phenotypes was not demonstrated in our study in which all of the included G6PD-deficient patients were presented with neonatal hyperbilirubinemia and acute hemolytic anemia, since the genotype-phenotype correlation is normally demonstrated in chronic nonspherocytic hemolytic anemia (CNSHA) G6PD-deficient individuals.ConclusionThis study characterizes the molecular heterogeneity of G6PD variants causing G6PD deficiency in Thai children. Our study demonstrated the efficiency of direct DNA sequencing which can identify 12 missense mutations in Thai children.