G6PD Deficiency: Imbalance Of Functional Dichotomy Contributing to the Severity of COVID-19

Mondal, Abir; Mukherjee, Soumyadeep; Dar, Waseem; Upadhyay, Prince; Ranganathan, Anand; Pati, Soumya; Singh, Shailja

doi:10.2217/fmb-2021-0299

Cited by 5 publications

(6 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have demonstrated that individuals with ADHD exhibited higher rates of infections including COVID-19 [25,26] with higher rates of severity [29,47] and complications [27]. Similarly, it was shown that G6PD-deficient individuals have a higher incidence of infectious diseases, indicating a predisposition to infections [40,41,45,46,48]. Our previous study showed that G6PD-deficient individuals had a higher risk of COVID-19 infection, of COVID-19 hospitalization, and of developing long-COVID [46].…”

Section: Discussionmentioning

confidence: 94%

“…The dysregulation of reactive oxygen species (ROS) represents a crucial mechanism that can contribute to a heightened and more severe inflammatory response in individuals, thereby increasing the symptomatic nature of infection diseases [39,45,46]. Studies have demonstrated that individuals with ADHD exhibited higher rates of infections including COVID-19 [25,26] with higher rates of severity [29,47] and complications [27].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder

Merzon,

Magen,

Ashkenazi

et al. 2023

Nutrients

View full text Add to dashboard Cite

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with potential relevance to Attention Deficit/Hyperactivity Disorder (ADHD). This study investigated this association. Methods: The clinical characteristics of 7473 G6PD-deficient patients and 29,892 matched case–controls (selected at a 1:4 ratio) from a cohort of 1,031,354 within the Leumit Health Services database were analyzed using Fisher’s exact test for categorical variables and the Mann–Whitney U test for continuous variables. Results: In total, 68.7% were male. The mean duration of follow-up was 14.3 ± 6.2 years at a mean age of 29.2 ± 22.3 years. G6PD deficiency was associated with an increased risk of being diagnosed with ADHD (Odds Ratio (OR) = 1.16 [95% CI, 1.08–1.25], p < 0.001), seeking care from adult neurologists (OR = 1.30 [95% CI, 1.22–1.38], p < 0.001), and consulting adult psychiatrists (OR = 1.12 [95% CI, 1.01–1.24], p = 0.048). The use of stimulant medications among G6PD-deficient individuals was 17% higher for the methylphenidate class of drugs (OR = 1.17 [95% CI, 1.08, 1.27], p < 0.001), and there was a 16% elevated risk for amphetamine use (OR = 1.16 [95% CI, 1.03, 1.37], p = 0.047). Conclusions: G6PD deficiency signals an increased risk of ADHD diagnosis, more severe presentations of ADHD and a greater need for psychiatric medications to treat ADHD.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder

Merzon,

Magen,

Ashkenazi

et al. 2023

Nutrients

View full text Add to dashboard Cite

show abstract

“…Our study only focused on the ubiquitination of MAVS and the TRAF family of the MAVS signalosome. (iii) Patients with deficiencies in the G6PD or GFPT2 were susceptible to recurrent infections and sepsis 33 , 34 . It remains unknown whether using a series of pharmacological, enhancing G6PD or GFPT2 activity would enhance antiviral response in patients.…”

Section: Discussionmentioning

confidence: 99%

MAVS integrates glucose metabolism and RIG-I-like receptor signaling

He,

Huang,

Nie

et al. 2023

Nat Commun

View full text Add to dashboard Cite

MAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling in mitochondria, peroxisomes, and mitochondria-associated ER membranes (MAMs). However, the role of MAVS in glucose metabolism and RLR signaling cross-regulation and how these signaling pathways are coordinated among these organelles have not been defined. This study reports that RLR action drives a switch from glycolysis to the pentose phosphate pathway (PPP) and the hexosamine biosynthesis pathway (HBP) through MAVS. We show that peroxisomal MAVS is responsible for glucose flux shift into PPP and type III interferon (IFN) expression, whereas MAMs-located MAVS is responsible for glucose flux shift into HBP and type I IFN expression. Mechanistically, peroxisomal MAVS interacts with G6PD and the MAVS signalosome forms at peroxisomes by recruiting TNF receptor-associated factor 6 (TRAF6) and interferon regulatory factor 1 (IRF1). By contrast, MAMs-located MAVS interact with glutamine-fructose-6-phosphate transaminase, and the MAVS signalosome forms at MAMs by recruiting TRAF6 and TRAF2. Our findings suggest that MAVS mediates the interaction of RLR signaling and glucose metabolism.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Several studies have suggested that G6PD-deficient individuals may be more predisposed to specific autoimmune diseases (Dore et al, 2023; Saha et al, 1982), infections (Abu-Osba et al, 1989; Mondal et al, 2022; Rostami-Far et al, 2016) and diabetes mellitus (Lai et al, 2017; Saha, 1979). Associations were found between G6PD deficiency and cardiovascular risk (Cocco et al, 1998; Dore et al, 2021; Meloni et al, 2008; Pes et al, 2019) in conflicting directions.…”

Section: Introductionmentioning

confidence: 99%

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Long-Term Risk of Immune-Related diseases

Israel

Schäffer

Berkovitch

et al. 2023

Preprint

View full text Add to dashboard Cite

BACKGROUND Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive enzymatic disorder, particularly prevalent in Africa, Asia and the Middle East. In the US, about 14% of black men are affected. Individuals with G6PD deficiency are often asymptomatic but may develop hemolysis following an infection or upon consumption of specific medications. Despite some evidence that G6PD deficiency affects the immune system, the long-term health risks associated with G6PD deficiency had not been studied in a large population. METHODS In this retrospective cohort study, health records from G6PD deficient individuals were compared to matched controls in a national healthcare provider in Israel (Leumit Health Services). Rates of infectious diseases, allergic conditions and autoimmune disorders were compared between groups. RESULTS The cohort included 7,473 G6PD deficient subjects (68.7% men) matched with 29,892 control subjects (4:1 ratio) of the same age, gender, socioeconomic status and ethnic group, followed during 14.3 years (standard deviation 6.2). Significantly increased rates for autoimmune disorders, infectious diseases and allergic conditions were observed throughout this period. Notable increases were observed for rheumatoid arthritis (OR 2.41, p<0.001), systemic lupus erythematosus (OR 4.56, p<0.001), scleroderma (OR 6.87, p<0.001), pernicious anemia (OR=18.70, P<0.001), fibromyalgia (OR 1.98, p<0.001), Graves' disease (OR 1.46, P=0.001), and Hashimoto's thyroiditis (OR 1.26, P=0.001). These findings were corroborated with elevated rates of positive autoimmune serology and higher rates of treatment with medications commonly used to treat autoimmune conditions in the G6PD deficient group. CONCLUSION G6PD deficient individuals suffer from higher rates of autoimmune disorders, infectious diseases, and allergic conditions.

show abstract

G6PD Deficiency: Imbalance Of Functional Dichotomy Contributing to the Severity of COVID-19

Cited by 5 publications

References 80 publications

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder

MAVS integrates glucose metabolism and RIG-I-like receptor signaling

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Long-Term Risk of Immune-Related diseases

Contact Info

Product

Resources

About