دورية أكاديمية
Genetic analysis and molecular basis of G6PD deficiency among malaria patients in Thailand: implications for safe use of 8-aminoquinolines
| العنوان: | Genetic analysis and molecular basis of G6PD deficiency among malaria patients in Thailand: implications for safe use of 8-aminoquinolines |
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| المؤلفون: | Boonyuen, Usa, Jacob, Beatriz Aira C., Wongwigkan, Jutamas, Chamchoy, Kamonwan, Singha-art, Natsamon, Pengsuk, Natnicha, Songdej, Duantida, Adams, Emily, Edwards, Thomas, Chamnanchanunt, Supat, Amran, Syazwani Itri, Latif, Nurriza Ab, Louis, Naveen Eugene, Chandran, Shamini |
| المصدر: | Malaria Journal, Vol 23, Issue 1, p. 38. |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2024 |
| المجموعة: | LSTM Online Archive (Liverpool School of Tropical Medicine) |
| مصطلحات موضوعية: | WC 750 Malaria |
| الوصف: | Background: It was hypothesized that glucose-6-phosphate dehydrogenase (G6PD) deficiency confers a protective effect against malaria infection, however, safety concerns have been raised regarding haemolytic toxicity caused by radical cure with 8-aminoquinolines in G6PD-deficient individuals. Malaria elimination and control are also complicated by the high prevalence of G6PD deficiency in malaria-endemic areas. Hence, accurate identification of G6PD deficiency is required to identify those who are eligible for malaria treatment using 8-aminoquinolines. Methods: The prevalence of G6PD deficiency among 408 Thai participants diagnosed with malaria by microscopy (71), and malaria-negative controls (337), was assessed using a phenotypic test based on water-soluble tetrazolium salts. High-resolution melting (HRM) curve analysis was developed from a previous study to enable the detection of 15 common missense, synonymous and intronic G6PD mutations in Asian populations. The identified mutations were subjected to biochemical and structural characterisation to understand the molecular mechanisms underlying enzyme deficiency. Results: Based on phenotypic testing, the prevalence of G6PD deficiency (< 30% activity) was 6.13% (25/408) and intermediate deficiency (30–70% activity) was found in 15.20% (62/408) of participants. Several G6PD genotypes with newly discovered double missense variants were identified by HRM assays, including G6PD Gaohe + Viangchan, G6PD Valladolid + Viangchan and G6PD Canton + Viangchan. A significantly high frequency of synonymous (c.1311C>T) and intronic (c.1365-13T>C and c.486-34delT) mutations was detected with intermediate to normal enzyme activity. The double missense mutations were less catalytically active than their corresponding single missense mutations, resulting in severe enzyme deficiency. While the mutations had a minor effect on binding affinity, structural instability was a key contributor to the enzyme deficiency observed in G6PD-deficient individuals. Conclusions: With ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://archive.lstmed.ac.uk/23962/1/12936_2024_Article_4864.pdfTest; Boonyuen, Usa, Jacob, Beatriz Aira C., Wongwigkan, Jutamas, Chamchoy, Kamonwan, Singha-art, Natsamon, Pengsuk, Natnicha, Songdej, Duantida, Adams, Emily orcid:0000-0002-0816-2835 , Edwards, Thomas, Chamnanchanunt, Supat, Amran, Syazwani Itri, Latif, Nurriza Ab, Louis, Naveen Eugene and Chandran, Shamini (2024) 'Genetic analysis and molecular basis of G6PD deficiency among malaria patients in Thailand: implications for safe use of 8-aminoquinolines'. Malaria Journal, Vol 23, Issue 1, p. 38. |
| DOI: | 10.1186/s12936-024-04864-8 |
| الإتاحة: | https://doi.org/10.1186/s12936-024-04864-8Test https://archive.lstmed.ac.uk/23962Test/ https://archive.lstmed.ac.uk/23962/1/12936_2024_Article_4864.pdfTest |
| حقوق: | cc_by_4 |
| رقم الانضمام: | edsbas.C827604E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12936-024-04864-8 |
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