Genetic Variants of Glucose-6-Phosphate Dehydrogenase and Their Associated Enzyme Activity: A Systematic Review and Meta-Analysis
Year: 2022
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Low glucose-6-phosphate dehydrogenase enzyme (G6PD) activity is a key determinant of drug-induced haemolysis. More than 230 clinically relevant genetic variants have been described. We investigated the variation in G6PD activity within and between different genetic variants. In this systematic review, individual patient data from studies reporting G6PD activity measured by spectrophotometry and corresponding the G6PD genotype were pooled (PROSPERO: CRD42020207448). G6PD activity was converted into percent normal activity applying study-specific definitions of 100%. In total, 4320 individuals from 17 studies across 10 countries were included, where 1738 (40.2%) had one of the 24 confirmed G6PD mutations, and 61 observations (3.5%) were identified as outliers. The median activity of the hemi-/homozygotes with A-(c.202G>A/c.376A>G) was 29.0% (range: 1.7% to 76.6%), 10.2% (range: 0.0% to 32.5%) for Mahidol, 16.9% (range 3.3% to 21.3%) for Mediterranean, 9.0% (range: 2.9% to 23.2%) for Vanua Lava, and 7.5% (range: 0.0% to 18.3%) for Viangchan. The median activity in heterozygotes was 72.1% (range: 16.4% to 127.1%) for A-(c.202G>A/c.376A>G), 54.5% (range: 0.0% to 112.8%) for Mahidol, 37.9% (range: 20.7% to 80.5%) for Mediterranean, 53.8% (range: 10.9% to 82.5%) for Vanua Lava, and 52.3% (range: 4.8% to 78.6%) for Viangchan. A total of 99.5% of hemi/homozygotes with the Mahidol mutation and 100% of those with the Mediterranean, Vanua Lava, and Viangchan mutations had <30% activity. For A-(c.202G>A/c.376A>G), 55% of hemi/homozygotes had <30% activity. The G6PD activity for each variant spanned the current classification thresholds used to define clinically relevant categories of enzymatic deficiency.
Source: Pathogens
Authors: Daniel A. Pfeffer, Ari Winasti Satyagraha, Arkasha Sadhewa, Mohammad Shafiul Alam, Germana Bancone, Yap Boum, Marcelo Brito, Liwang Cui, Zeshuai Deng, Gonzalo J. Domingo, Yongshu He, Wasif A. Khan, Mohammad Golam Kibria, Marcus Lacerda, Didier Menard, Wuelton Monteiro, Sampa Pal, Sunil Parikh, Arantxa Roca-Feltrer, Michelle Roh, Mahmoud M. Sirdah, Duoquan Wang, Qiuying Huang, Rosalind E. Howes, Ric N. Price, Benedikt Ley
Institutions: Charles Darwin University, Menzies School of Health Research, Eijkman Institute for Molecular Biology, International Centre for Diarrhoeal Disease Research, Mahidol University, University of Oxford, Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Médecins Sans Frontières, Mbarara University of Science and Technology, Fundação de Medicina Tropical, University of South Florida, Kunming Medical University, Program for Appropriate Technology in Health, Inserm, Institut Pasteur, Université de Strasbourg, Yale University, Malaria Consortium, University of California, San Francisco, Al-Azhar University – Gaza, National Institute for Parasitic Diseases, Shanghai Jiao Tong University, Xiamen University, FIND
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,303
Awards: G1044130170, G128292601, G2232654402, G234121574, G2652538284, G2734856756, G2750236556, Menzies School of Health Research - to expand the safe and effective use of primaquine for radical cure in diverse locations, G3570303064, G3916761993, G4399831822, G4497626964, The role of innate immunity in respiratory viral infection in the elderly, G4811193640, G5142468444, G6037456758, G7381777635, Improving the treatment of Plasmodium vivax, Yale Clinical and Translational Science Award
OpenAlex ID: W4296097914