Glucose-6-phosphate dehydrogenase deficiency and risk of diabetes: a systematic review and meta-analysis

Lai, Yin Key; Lai, Nai Ming; Lee, Shaun Wen Huey

doi:10.1007/s00277-017-2945-6

Cited by 29 publications

(37 citation statements)

References 17 publications

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“…117 MECP2 binds to methylated DNA and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (15q24.2 [MIM: 607776]) ( Figure S14). Lai et al 118 reported meta-results that T2D-affected case subjects with G6PD deficiency had two times higher odds of developing diabetes than unaffected control subjects. 119 Furthermore, G6PD protein has a weak score of 1 out of 5 to be found in MT.…”

Section: Mtdna and Metabolic Disease Associationsmentioning

confidence: 99%

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Kraja¹,

Liu

Fetterman

et al. 2019

The American Journal of Human Genetics

113

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Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNAþ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p % 5EÀ04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p % 1EÀ03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p % 1EÀ06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis-and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

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Section: Mtdna and Metabolic Disease Associationsmentioning

confidence: 99%

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Kraja¹,

Liu

Fetterman

et al. 2019

The American Journal of Human Genetics

113

View full text Add to dashboard Cite

show abstract

“…Activity of alternative pathways provides robustness of NADPH supply and to some extent compensates deficit of PPP flux in patients with glucose-6 phosphate dehydrogenase (G6PD) deficiency, the most common genetic disease in humans [18]. Patients with G6PD deficiency generally have no symptoms and their lifespan is not affected by disease, but it was shown that in addition to increased hemolysis they are less resistant to some poisonings [18] and have higher risk of diabetes and metabolic syndrome [19]. Glucose-6 phosphate (G6P) is an exclusive substrate for G6PD, a rate limiting enzyme of PPP and in human organism can be supplied from extracellular space in the form of glucose, then phosphorylated by hexokinase.…”

Section: Basic Overview Of Glucose Metabolism and Its Role In Maintenmentioning

confidence: 99%

Glucose as a Major Antioxidant: When, What for and Why It Fails?

Cherkas¹,

Holota²,

Mdzinarashvili³

et al. 2020

Preprint

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A human organism depends on stable glucose blood levels in order to maintain the metabolic needs. Glucose is considered as the most important energy source and glycolysis is postulated as a backbone pathway. However, when glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. PPP generates and maintains levels of NADPH needed for reduction of oxidized glutathione and protein thiols, synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. Flux of glucose into a PPP, particularly under extreme oxidative and toxic challenges is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP+ that is required for activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload and provides new insights into positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

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“…G6PD deficiency is the most common genetic human disease [18]. Since G6PD is a gateway to such an important metabolic pathway as PPP, dramatic consequences to the patients could be expected.…”

Section: Glucose-6 Phosphate Dehydrogenase Deficiencymentioning

confidence: 99%

“…It is likely that the other structural and functional interactions may exist in the cells in order to couple synergistic metabolic processes in response to oxidative stress. Activity of alternative pathways provides robustness of NADPH supply and to some extent compensates deficit of PPP flux in patients with glucose-6 phosphate dehydrogenase (G6PD) deficiency, the most common genetic disease in humans [18]. Patients with G6PD deficiency generally have no symptoms and their lifespan is not affected by disease, but it was shown that in addition to increased hemolysis they are less resistant to some poisonings [18] and have higher risk of diabetes and metabolic syndrome [19].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glucose as a Major Antioxidant: When, What for and Why It Fails?

Cherkas¹,

Holota²,

Mdzinarashvili³

et al. 2019

Preprint

View full text Add to dashboard Cite

A human organism depends on stable glucose blood levels in order to maintain the metabolic needs. Glucose is considered as the most important energy source and glycolysis is postulated as a backbone pathway. However, when glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of pentose phosphate pathway (PPP) glucose is essential and cannot be substituted for by other metabolites. PPP generates and maintains levels of NADPH needed for reduction of oxidized glutathione and protein thiols, synthesis of lipids and DNA as well as for xenobiotics detoxification, regulatory redox signaling and counteracting infections. Flux of glucose into a PPP, particularly under extreme oxidative and toxic challenges is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP+ that is required for activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidence explains disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload and provides new insights into positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

show abstract

Glucose-6-phosphate dehydrogenase deficiency and risk of diabetes: a systematic review and meta-analysis

Cited by 29 publications

References 17 publications

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Glucose as a Major Antioxidant: When, What for and Why It Fails?

Glucose as a Major Antioxidant: When, What for and Why It Fails?

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