The ethnogeographic variability of genetic factors underlying G6PD deficiency

Koromina, Maria; Pandi, Maria Theodora; Spek, Peter J. van der; Patrinos, George P.; Lauschke, Volker M.

doi:10.1016/j.phrs.2021.105904

Cited by 19 publications

(14 citation statements)

References 60 publications

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“…G6PD de ciency is a common enzyme abnormality that a ects approximately 5% of the world´s population and causes some diseases related to erythrocytes [24]. Some Anemia Anemia mutations on the G6PD gene are being investigated to be associated with this deficiency of the G6PD enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization and Genotype-Phenotype Correlation of G6PD Mutations in Five Ethnicities of Northern Vietnam

Ngo

Tran

et al. 2022

Anemia

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder and is caused by G6PD gene mutations. To date, more than 400 variants in the G6PD gene have been discovered, and about 160 identified variants are associated with a significant decrease in the G6PD enzyme activity. However, the molecular characterization and epidemiological study of G6PD deficiency are still limited in Vietnam. Therefore, we conducted this study to determine the G6PD variants among the Vietnamese populations and evaluate their correlation to G6PD enzyme activity. A total of 339 patients (302 males and 37 females) were enrolled in this study. The G6PD variants were identified by Sanger sequencing. Our results indicate that males are more severely deficient in G6PD than females. This enzyme activity in males (1.27 ± 1.06 IU/g·Hb) is significantly lower than in females (2.98 ± 1.57 IU/g·Hb) ( p < 0.0001 ). The enzyme activity of the heterozygous-homozygous females and heterozygous females-hemizygous males was found to be significantly different ( p < 0.05 ), which is interpreted due to random X-inactivation. For G6PD molecular characteristics, Viangchan (c.871G>A), Canton (c.1376G>T) and Kaiping (c.1388G>A) variants were the most dominant, accounting for 24.48%, 17.70%, and 22.42%, respectively, whereas the highest frequency of complex variants was observed in Viangchan/Silent with 20.35%. In terms of G6PD activity, the Union variant presented the lowest mean value (1.03 IU/g·Hb) compared to the other variants ( p < 0.05 ). Computational analysis using Polyphen-2 tool investigated that all variants were relative to G6PD deficiency and separated the levels as benign and damaged. The result will establish effective methods to screen G6PD variants in Vietnam.

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization and Genotype-Phenotype Correlation of G6PD Mutations in Five Ethnicities of Northern Vietnam

Ngo

Tran

et al. 2022

Anemia

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“…Notably, G6PD is located on the X-chromosome and thus primarily impacts hemizygous males and homozygous females, whereas among heterozygous females only around 8-20% exhibit clinically relevant levels of reduced G6PD activity (Chu et al 2018;Dechyotin et al 2021;Johnson et al 2009;Satyagraha et al 2021). G6PD deficiency is most common in Africa, followed by Southeast Asia and the Middle East (Koromina et al 2021;Nkhoma et al 2009). While overall disease prevalence might be similar between these regions, the genetic basis of G6PD differs drastically (Table 6).…”

Section: G6pdmentioning

confidence: 99%

“…G6PD deficiency is most common in Africa, followed by Southeast Asia and the Middle East (Koromina et al 2021 ; Nkhoma et al 2009 ). While overall disease prevalence might be similar between these regions, the genetic basis of G6PD deficiency differs drastically (Table 6 ).…”

Section: G6pdmentioning

confidence: 99%

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Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

Zhou

Lauschke

2021

Hum Genet

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Both safety and efficacy of medical treatment can vary depending on the ethnogeographic background of the patient. One of the reasons underlying this variability is differences in pharmacogenetic polymorphisms in genes involved in drug disposition, as well as in drug targets. Knowledge and appreciation of these differences is thus essential to optimize population-stratified care. Here, we provide an extensive updated analysis of population pharmacogenomics in ten pharmacokinetic genes (CYP2D6, CYP2C19, DPYD, TPMT, NUDT15 and SLC22A1), drug targets (CFTR) and genes involved in drug hypersensitivity (HLA-A, HLA-B) or drug-induced acute hemolytic anemia (G6PD). Combined, polymorphisms in the analyzed genes affect the pharmacology, efficacy or safety of 141 different drugs and therapeutic regimens. The data reveal pronounced differences in the genetic landscape, complexity and variant frequencies between ethnogeographic groups. Reduced function alleles of CYP2D6, SLC22A1 and CFTR were most prevalent in individuals of European descent, whereas DPYD and TPMT deficiencies were most common in Sub-Saharan Africa. Oceanian populations showed the highest frequencies of CYP2C19 loss-of-function alleles while their inferred CYP2D6 activity was among the highest worldwide. Frequencies of HLA-B*15:02 and HLA-B*58:01 were highest across Asia, which has important implications for the risk of severe cutaneous adverse reactions upon treatment with carbamazepine and allopurinol. G6PD deficiencies were most frequent in Africa, the Middle East and Southeast Asia with pronounced differences in variant composition. These variability data provide an important resource to inform cost-effectiveness modeling and guide population-specific genotyping strategies with the goal of optimizing the implementation of precision public health.

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“…G6PD deficiency, a prevalent human enzyme disorder, arises from an inherited mutation in an X-linked gene [ 15 ]. The investigation, through genetic variation screening, revealed that the highest occurrence of this condition among males was observed in Africans, followed by Asians, Middle Easterners, and Europeans [ 16 ]. Carriers of G6PD deficiency are mostly asymptomatic but are also at great risk of acute hemolytic anemia after exposure to some drugs or infection [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Incidence Trends of Inherited Anemias at the Global, Regional, and National Levels Over Three Decades

Tang,

Zhang,

Liu

et al. 2023

J Epidemiol Glob Health

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Inherited anemia continues to pose a significant public health concern on a global scale, owing to its extensive geographical prevalence, substantial patient population, and profound ramifications. Here, we investigated detailed information on inherited anemias (including thalassemias, thalassemias trait, sickle cell disease, sickle cell trait, G6PD deficiency, and G6PD trait) for the period 1990–2019 from the Global Burden of Disease study. Over the course of three decades, there has been a persistent rise in the incidence of inherited anemias worldwide, culminating in a total of 44,896,026 incident cases in 2019. However, the prevalence of inherited anemias has exhibited a consistent downward trend over successive years. Significantly, these inherited anemias primarily impact females, exhibiting a male-to-female ratio of 1:1.88. Among males, the most prevalent inherited anemia is G6PD deficiency, whereas G6PD trait prevails among females. The incidence rates of inherited anemias and their temporal trend exhibited significant variations across different regions, with Central Sub-Saharan Africa displaying the highest incidence rates and Central Latin America experiencing the most substantial decline. The findings of this study suggest a significant correlation between the Socio-Demographic index (SDI) and incidence rates of inherited anemias, particularly in regions with lower SDI levels such as Africa and South Asia. These results contribute valuable insights for the analysis of global trends in the burden of inherited anemias.

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The ethnogeographic variability of genetic factors underlying G6PD deficiency

Cited by 19 publications

References 60 publications

Molecular Characterization and Genotype-Phenotype Correlation of G6PD Mutations in Five Ethnicities of Northern Vietnam

Molecular Characterization and Genotype-Phenotype Correlation of G6PD Mutations in Five Ethnicities of Northern Vietnam

Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

Incidence Trends of Inherited Anemias at the Global, Regional, and National Levels Over Three Decades

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