PREVALENCE AND MOLECULAR CHARACTERIZATION OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY IN FEMALES FROM PREVIOUSLY MALARIA ENDEMIC REGIONS IN NORTHEASTERN THAILAND AND IDENTIFICATION OF A NOVEL G6PD VARIANT

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked enzymopathy, highly prevalent in areas where malaria is or has been endemic. Prevalence of G6PD deficiency and characterization of G6PD variants in females from previously malaria endemic areas of northeast Thailand remain unstudied. Methods: Prevalence of G6PD deficiency was determined by a fluorescent spot test (FST) and multiplex allele specific (AS)- and restriction fragment length polymorphic (RFLP)-PCR developed for detection of common G6PD variants in the Thai population. Results: Prevalence of G6PD deficiency in female samples (n = 355) was 18% by FST and 27% by PCR-based genotyping. The most common variant was G6PD Viangchan (54%), followed by G6PD Canton (11%) and G6PD Union (11%); in addition, a novel heterozygous variant, G6PD Khon Kaen (c.305T>C, p.F102S located in the coenzyme-binding domain), was identified. The majority (75%) of G6PD activities of heterozygotes were within the intermediate deficiency range (30-80% of median normal enzyme activity). Conclusion: High prevalence of G6PD deficiency was present in females from northeast Thailand, the majority being due to heterozygosity of G6PD variants. The findings will have a bearing on an inclusion of primaquine in antimalarial-based policies for malaria elimination in populations with high prevalence in G6PD deficiency.

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Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients of Chinese descent and identification of new base substitutions in the human G6PD gene

Blood ◽

10.1182/blood.v81.8.2150.2150 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2150-2154 ◽

Cited By ~ 40

Author(s):

DT Chiu ◽

L Zuo ◽

L Chao ◽

E Chen ◽

E Louie ◽

...

Keyword(s):

G6pd Deficiency ◽

Point Mutations ◽

Nucleotide Substitutions ◽

New Findings ◽

G6pd Gene ◽

High Prevalence ◽

Chinese Descent ◽

Glucose 6 Phosphate Dehydrogenase ◽

Sequencing Procedure

Abstract The underlying DNA changes associated with glucose-6-phosphate dehydrogenase (G6PD)-deficient Asians have not been extensively investigated. To fill this gap, we sequenced the G6PD gene of 43 G6PD- deficient Chinese whose G6PD was well characterized biochemically. DNA samples were obtained from peripheral blood of these individuals for sequencing using a direct polymerase chain reaction (PCR) sequencing procedure. From these 43 samples, we have identified five different types of nucleotide substitutions in the G6PD gene: at cDNA 1388 from G to A (Arg to His); at cDNA 1376 from G to T (Arg to Leu); at cDNA 1024 from C to T (Leu to Phe); at cDNA 392 from G to T (Gly to Val); at cDNA 95 from A to G (His to Arg). These five nucleotide substitutions account for over 83% of our 43 G6PD-deficient samples and these substitutions have not been reported in non-Asians. The substitutions found at cDNA 392 and cDNA 1024 are new findings. The substitutions at cDNA 1376 and 1388 account for over 50% of the 43 samples examined indicating a high prevalence of these two alleles among G6PD-deficient Chinese. Our findings add support to the notion that diverse point mutations may account largely for much of the phenotypic heterogeneity of G6PD deficiency.

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Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients of Chinese descent and identification of new base substitutions in the human G6PD gene

Blood ◽

10.1182/blood.v81.8.2150.bloodjournal8182150 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2150-2154

Author(s):

DT Chiu ◽

L Zuo ◽

L Chao ◽

E Chen ◽

E Louie ◽

...

Keyword(s):

G6pd Deficiency ◽

Point Mutations ◽

Nucleotide Substitutions ◽

New Findings ◽

G6pd Gene ◽

High Prevalence ◽

Chinese Descent ◽

Glucose 6 Phosphate Dehydrogenase ◽

Sequencing Procedure

The underlying DNA changes associated with glucose-6-phosphate dehydrogenase (G6PD)-deficient Asians have not been extensively investigated. To fill this gap, we sequenced the G6PD gene of 43 G6PD- deficient Chinese whose G6PD was well characterized biochemically. DNA samples were obtained from peripheral blood of these individuals for sequencing using a direct polymerase chain reaction (PCR) sequencing procedure. From these 43 samples, we have identified five different types of nucleotide substitutions in the G6PD gene: at cDNA 1388 from G to A (Arg to His); at cDNA 1376 from G to T (Arg to Leu); at cDNA 1024 from C to T (Leu to Phe); at cDNA 392 from G to T (Gly to Val); at cDNA 95 from A to G (His to Arg). These five nucleotide substitutions account for over 83% of our 43 G6PD-deficient samples and these substitutions have not been reported in non-Asians. The substitutions found at cDNA 392 and cDNA 1024 are new findings. The substitutions at cDNA 1376 and 1388 account for over 50% of the 43 samples examined indicating a high prevalence of these two alleles among G6PD-deficient Chinese. Our findings add support to the notion that diverse point mutations may account largely for much of the phenotypic heterogeneity of G6PD deficiency.

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Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in the Shenzhen Population

Human Heredity ◽

10.1159/000516808 ◽

2021 ◽

pp. 1-7

Author(s):

Jian Gao ◽

Sheng Lin ◽

Shiguo Chen ◽

Qunyan Wu ◽

Kaifeng Zheng ◽

...

Keyword(s):

G6pd Deficiency ◽

Amplification Refractory Mutation System ◽

Gene Variants ◽

Coding Region ◽

G6pd Gene ◽

Mutation System ◽

Hotspot Mutations ◽

Glucose 6 Phosphate Dehydrogenase ◽

Generation Sequencing

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. This study aimed to characterize the G6PD gene variant distribution in Shenzhen of Guangdong province. Methods: A total of 33,562 individuals were selected at the hospital for retrospective analysis, of which 1,213 cases with enzymatic activity-confirmed G6PD deficiency were screened for G6PD gene variants. Amplification refractory mutation system PCR was first used to screen the 6 dominant mutants in the Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). If the 6 hotspot variants were not found, next-generation sequencing was then performed. Finally, Sanger sequencing was used to verify all the mutations. Results: The incidence of G6PD deficiency in this study was 3.54%. A total of 26 kinds of mutants were found in the coding region, except for c.-8-624T>C, which was in the noncoding region. c.1376G>T and c.1388G>A, both located in exon 12, were the top 2 mutants, accounting for 68.43% of all individuals. The 6 hotspot mutations had a cumulative proportion of 94.02%. Conclusions: This study provided detailed characteristics of G6PD gene variants in Shenzhen, and the results would be valuable to enrich the knowledge of G6PD deficiency.

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Prevalence and Genetic Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in Anemic Subjects from Uttar Pradesh, India

Journal of Pediatric Genetics ◽

10.1055/s-0039-1677729 ◽

2019 ◽

Vol 08 (02) ◽

pp. 047-053 ◽

Cited By ~ 1

Author(s):

Poonam Tripathi ◽

Sarita Agarwal ◽

Srinivasan Muthuswamy

Keyword(s):

G6pd Deficiency ◽

Dehydrogenase Deficiency ◽

Genetic Characterization ◽

Gene Mutations ◽

Uttar Pradesh ◽

Chromosome X ◽

G6pd Gene ◽

Glucose 6 Phosphate Dehydrogenase ◽

Fluorescent Spot

AbstractGlucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. It affects approximately 400 million people worldwide. The purpose of this study was to detect the prevalence of G6PD deficiency and G6PD gene mutations in the hospital-based settings in patients referred for suspected G6PD deficiency. A qualitative fluorescent spot test and dichlorophenol-indolphenol (DCIP) test were performed. G6PD-deficient, positive samples were further processed for mutation analysis by Sanger sequencing. Out of 1,069 cases, 95 (8.8%) were detected as G6PD deficient (by DCIP test) and were sent for molecular analysis. The G6PD Mediterranean mutation (563C > T) is the most common variant among G6PD-deficient individuals followed by the Coimbra (592C→T) and Orissa (131C→G) variants. We concluded that all symptomatic patients (anemic or jaundiced) should be investigated for G6PD deficiency. Our findings will inform our population screening approach and help provide better management for G6PD-deficient patients.

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Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency by natural and amplification created restriction sites: five mutations account for most G6PD deficiency cases in Taiwan

Blood ◽

10.1182/blood.v80.4.1079.1079 ◽

1992 ◽

Vol 80 (4) ◽

pp. 1079-1082 ◽

Cited By ~ 40

Author(s):

JG Chang ◽

SS Chiou ◽

LI Perng ◽

TC Chen ◽

TC Liu ◽

...

Keyword(s):

G6pd Deficiency ◽

Restriction Enzymes ◽

Common Mutation ◽

Simple Method ◽

Molecular Defects ◽

G6pd Gene ◽

Restriction Sites ◽

Glucose 6 Phosphate Dehydrogenase ◽

Deficiency Cases

Abstract We have developed a rapid and simple method to diagnose the molecular defects of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Chinese in Taiwan. This method involves the selective amplification of a DNA fragment from human G6PD gene with specific oligonucleotide primers followed by digestion with restriction enzymes that recognize artificially created or naturally occurring restriction sites. Ninety- four Chinese males with G6PD deficiency were studied. The results show that 50% (47 of 94) were G to T mutation at nucleotide (nt) 1376, 21.3% (20 of 94) were G to A mutation at nt 1388, 7.4% (7 of 94) were A to G mutation at nt 493, 7.4% (7 of 94) were A to G mutation at nt 95, 4.2% (4 of 94) were C to T mutation at nt 1024, 1.1% (1 of 94) was G to T mutation at nt 392, and 1.1% (1 of 94) was G to A mutation at nt 487. These results show that the former five mutations account for more than 90% of G6PD deficiency cases in Taiwan. Aside from showing that G to T change at nt 1376 is the most common mutation, our research indicates that nt 493 mutation is a frequent mutation among Chinese in Taiwan. We compared G6PD activity among different mutations, without discovering significant differences between them.

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Genotypic glucose-6-phosphate dehydrogenase (G6PD) deficiency protects against Plasmodium falciparum infection in individuals living in Ghana

PLoS ONE ◽

10.1371/journal.pone.0257562 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257562

Author(s):

Linda Eva Amoah ◽

Kwame Kumi Asare ◽

Donu Dickson ◽

Joana Abankwa ◽

Abena Busayo ◽

...

Keyword(s):

G6pd Deficiency ◽

Malaria Prevalence ◽

Health Care Facilities ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Length Polymorphisms ◽

G6pd Gene ◽

High Prevalence ◽

Care Facilities ◽

Glucose 6 Phosphate Dehydrogenase

Introduction The global effort to eradicate malaria requires a drastic measure to terminate relapse from hypnozoites as well as transmission via gametocytes in malaria-endemic areas. Primaquine has been recommended for the treatment of P. falciparum gametocytes and P. vivax hypnozoites, however, its implementation is challenged by the high prevalence of G6PD deficient (G6PDd) genotypes in malaria endemic countries. The objective of this study was to profile G6PDd genotypic variants and correlate them with malaria prevalence in Ghana. Methods A cross-sectional survey of G6PDd genotypic variants was conducted amongst suspected malaria patients attending health care facilities across the entire country. Malaria was diagnosed using microscopy whilst G6PD deficiency was determined using restriction fragment length polymorphisms at position 376 and 202 of the G6PD gene. The results were analysed using GraphPad prism. Results A total of 6108 subjects were enrolled in the study with females representing 65.59% of the population. The overall prevalence of malaria was 36.31%, with malaria prevalence among G6PDd genotypic variants were 0.07% for A-A- homozygous deficient females, 1.31% and 3.03% for AA- and BA- heterozygous deficient females respectively and 2.03% for A- hemizygous deficient males. The odd ratio (OR) for detecting P. falciparum malaria infection in the A-A- genotypic variant was 0.0784 (95% CI: 0.0265–0.2319, p<0.0001). Also, P. malariae and P. ovale parasites frequently were observed in G6PD B variants relative to G6PD A- variants. Conclusion G6PDd genotypic variants, A-A-, AA- and A- protect against P. falciparum, P. ovale and P. malariae infection in Ghana.

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Fine mapping of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency in rural area of South West Odisha using the clinical, hematological and molecular approach

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2020.015 ◽

2020 ◽

Vol 12 (1) ◽

pp. e2020015

Author(s):

Ravindra Kumar ◽

MPSS Singh ◽

Soumendu Mahapatra ◽

Sonam Chourasia ◽

Malay Kumar Tripathi ◽

...

Keyword(s):

G6pd Deficiency ◽

Clinical History ◽

South West ◽

Normal Individuals ◽

Pcr Rflp ◽

History Of ◽

Tribal Populations ◽

Glucose 6 Phosphate Dehydrogenase ◽

National Prevalence

Introduction: The aim of the study was to enumerate the clinical, hematological and molecular spectrum of G6PD deficiency in malaria endemic regions of south west Odisha. Methods: Diagnosis of G6PD deficiency was made by using the Di-chloroindophenol Dye test in from two south west districts (Kalahandi and Rayagada) of Odisha State. Demographic and clinical history was taken from each individual using a pre-structured questionnaire. Molecular characterization of G6PD deficiency was done using PCR-RFLP and Sanger sequencing. Results: A total of 1981 individuals were screened, out of which 59 (2.97%) individuals were found G6PD deficient. Analysis revealed that G6PD deficiency was more in males (4.0%) as compared to females (2.3%). G6PD deficiency was significantly higher in tribal population (4.8%) as compared to non-tribal populations (2.4%) (p=0.012, OR=2.014, 95%CI =1.206-3.365). Individuals with history of malaria and G6PD deficiency have high risk of need of blood transfusion than G6PD normal individuals (p=0.026, OR=3.816, 95%CI=1.079-13.496). Molecular analysis revealed G6PD Orissa as the most common (88%) mutation 88% in the studied cohort. G6PD Kaiping (n=3), G6PD Coimbra (n=2) and G6PD Union (n=1) were also identified in studied cohort. Conclusion: The cumulative prevalence of G6PD deficiency the present is below the estimated national prevalence. G6PD deficiency was higher in tribes as compared to non-tribes. Rare G6PD Kaiping and G6PD Union variants have been identified.

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Screening of Glucose-6-Phosphate Dehydrogenase Deficiency in Neonatal Hyperbilirubinaemia at 300-Bedded Pyin Oo Lwin General Hospital

Myanmar Health Sciences Research Journal ◽

10.34299/mhsrj.00952 ◽

2019 ◽

Vol 31 (3) ◽

pp. 226-232

Keyword(s):

General Hospital ◽

G6pd Deficiency ◽

Serum Bilirubin Level ◽

Total Serum ◽

Cross Sectional ◽

Qualitative And Quantitative ◽

Quantitative Measurements ◽

Human Enzyme ◽

High Prevalence ◽

Glucose 6 Phosphate Dehydrogenase

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human enzyme deficiencies in the world. It is particularly common in populations living in malaria-endemic areas, affecting more than 400 million people worldwide. This hospital- and laboratory-based, cross-sectional descriptive study was conducted with the aim of determining the prevalence of G6PD deficiency among 200 newborns at 300-bedded Pyin Oo Lwin General Hospital during January to March 2017. The participants were 103 girls (58.5%) and 97 boys (41.5%). Both qualitative and quantitative measurements by using Brewer's method and G-SIX kit method were applied for diagnosis of G6PD deficiency. Total serum bilirubin level was measured by Bilirubinometer. Of the 200 newborns, 21(10.5%) were G6PD deficient. The overall prevalence of G6PD deficiency was 10.5% (21/200) and male was predominant than female (17.5% vs 3.9%). Out of 10.5% (21/100)G6PD deficient newborns, 5(23.8%) and 16(76.2%) were mild and moderate G6PD deficiency, respectively. Regarding hyperbilirubinaemia, 9(42.9%), 3(14.3%), 2(19.0%) and 5(23.8%) were severe, moderate and mild hyperbilirubinaemia and normal bilirubin, respectively. This study showed that a significant correlation between the severity of hyperbili- rubinaemia and G6PD activity (p <0.05). Taking into consideration of the above results, the high prevalence can be useful for providing appropriate prevention and early treatment of complications in routine neonatal screening in this area.

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