G6PD Deficiency and Hemoglobinopathies: Molecular Epidemiological Characteristics and Healthy Effects on Malaria Endemic Bioko Island, Equatorial Guinea

Lin, Min; Yang, Li; Xie, Dong De; Chen, Jiang Tao; Nguba, Santiago-m Monte; Ehapo, Carlos Sala; Zhan, Xia; Eyi, Juan Urbano Monsuy; Matesa, Rocio Apicante; Obono, Maximo Miko Ondo; Yang, Hui; Cheng, Ji Dong

doi:10.1371/journal.pone.0123991

Cited by 15 publications

(20 citation statements)

References 39 publications

(50 reference statements)

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“…G6PD enzymatic activity was measured within 12 h using a FST following the manufacturer’s instruction (Micky Ltd, Guangzhou, China). This kit is commonly used to screen G6PD deficiency in newborns in China and recently it was used in an epidemiological screen for G6PD deficiency in Equatorial Guinea [ 18 ]. In brief, blood was spotted on Whatman 903 filter paper, air dried, and immediately used for FST.…”

Section: Methodsmentioning

confidence: 99%

Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border

Yang

Liu

et al. 2015

PLoS ONE

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage. G6PD deficiency is particularly prevalent in historically malaria-endemic areas. Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients. In this study, we systematically evaluated the prevalence of G6PD deficiency in the Kachin (Jingpo) ethnic group along the China-Myanmar border and determined the underlying G6PD genotypes. We surveyed G6PD deficiency in 1770 adult individuals (671 males and 1099 females) of the Kachin ethnicity using a G6PD fluorescent spot test. The overall prevalence of G6PD deficiency in the study population was 29.6% (523/1770), among which 27.9% and 30.6% were males and females, respectively. From these G6PD deficient samples, 198 unrelated individuals (147 females and 51 males) were selected for genotyping at 11 known G6PD single nucleotide polymorphisms (SNPs) in Southeast Asia (ten in exons and one in intron 11) using a multiplex SNaPshot assay. Mutations with known association to a deficient phenotype were detected in 43.9% (87/198) of cases, intronic and synonymous mutations were detected alone in 34.8% (69/198) cases and no mutation were found in 21.2% (42/198) cases. Five non-synonymous mutations, Mahidol 487G>A, Kaiping 1388G>A, Canton 1376G>T, Chinese 4 392G>T, and Viangchan 871G>A were detected. Of the 87 cases with known deficient mutations, the Mahidol variant was the most common (89.7%; 78/87), followed by the Kaiping (8.0%; 7/87) and the Viangchan (2.2%; 2/87) variants. The Canton and Chinese 4 variants were found in 1.1% of these 87 cases. Among them, two females carried the Mahidol/Viangchan and Mahidol/Kaiping double mutations, respectively. Interestingly, the silent SNPs 1311C>T and IVS11nt93T>C both occurred in the same 95 subjects with frequencies at 56.4% and 23.5% in tested females and males, respectively (P<0.05). It is noteworthy that 24 subjects carrying the Mahidol mutation and two carrying the Kaiping mutation also carried the 1311C>T/IVS11nt93T>C SNPs. Further studies are needed to determine the enzyme levels of the G6PD deficient people and presence of additional G6PD mutations in the study population.

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Section: Methodsmentioning

confidence: 99%

Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border

Yang

Liu

et al. 2015

PLoS ONE

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“…More than 300 different mutations have been reported in the G6PD gene8; to date, the Human Gene Mutation Database (www.hgmd.cf.ac.uk/) has reported 202 mutations, with 68 pathogenic mutations that belong to Class I (WHO). The Mediterranean mutation (p.S188F) is the most prevalent among Arabs, with 90% frequency in Bahraini patients91011, 87.8% in Northern Iraqi males, 74.2% in Kuwait, and 53.6% in Jordan1213.…”

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confidence: 99%

Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World

Alasmar

Bux

et al. 2016

Sci Rep

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A systematic search was implemented using four literature databases (PubMed, Embase, Science Direct and Web of Science) to capture all the causative mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) in the 22 Arab countries. Our search yielded 43 studies that captured 33 mutations (23 missense, one silent, two deletions, and seven intronic mutations), in 3,430 Arab patients with G6PDD. The 23 missense mutations were then subjected to phenotypic classification using in silico prediction tools, which were compared to the WHO pathogenicity scale as a reference. These in silico tools were tested for their predicting efficiency using rigorous statistical analyses. Of the 23 missense mutations, p.S188F, p.I48T, p.N126D, and p.V68M, were identified as the most common mutations among Arab populations, but were not unique to the Arab world, interestingly, our search strategy found four other mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) that are unique to Arabs. These mutations were exposed to structural analysis and molecular dynamics simulation analysis (MDSA), which predicting these mutant forms as potentially affect the enzyme function. The combination of the MDSA, structural analysis, and in silico predictions and statistical tools we used will provide a platform for future prediction accuracy for the pathogenicity of genetic mutations.

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“…G6PD A‐: (V68M/N126D; c.202G>A/c.376A>G) was detected in the Bioko population ( n = 1,629) by PCR‐HRM (Lin et al, ). The genomic sequence of the G6PD gene (GRCh38.p12: GCF_000001405.38) from NCBI (://www.ncbi.nlm.nih.gov) was used in the analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Bioko Island, Equatorial Guinea, is one of the areas with the highest level of malaria transmission in the world (Cook et al, ). Our previous epidemiological screening of inherited blood disorders revealed the common G6PD deficiency genotype in the Bioko population was G6PD A‐ (V68M and N126D), with 8.7% prevalence (Lin et al, ). Thus, we carried out this investigation to search for the evidence of natural selection of the G6PD A‐ allele by Plasmodium falciparum in the African population on Bioko Island.…”

Section: Introductionmentioning

confidence: 99%

Evidence of positively selected G6PD A‐ allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island

Liang

Chen

et al. 2019

Molec Gen & Gen Med

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Background: Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme that protects red blood cells from oxidative damage. Although G6PD-deficient alleles appear to confer a protective effect of malaria, the link with clinical protection against Plasmodium infection is conflicting. Methods: A case-control study was conducted on Bioko Island, Equatorial Guinea and further genotyping analysis used to detect natural selection of the G6PD A-allele. Results: Our results showed G6PD A-allele could significantly reduce the risk of Plasmodium falciparum infection in male individuals (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.20-0.93; p < .05) and homozygous female individuals (AOR, 0.11; 95% CI, 0.01-0.84; p < .05). Additionally, the parasite densities were significantly different in the individuals with different G6PD A-alleles and individual levels of G6PD enzyme activity. The pattern of linkage disequilibrium and results of the long-range haplotype test revealed a strong selective signature in the region encompassing the G6PD A-allele over the past 6,250 years. The network of inferred haplotypes suggested a single origin of the G6PD A-allele in Africans.

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G6PD Deficiency and Hemoglobinopathies: Molecular Epidemiological Characteristics and Healthy Effects on Malaria Endemic Bioko Island, Equatorial Guinea

Cited by 15 publications

References 39 publications

Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border

Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border

Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World

Evidence of positively selected G6PD A‐ allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island

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