Molecular Characterization of Glucose-6-Phosphate Dehydrogenase deficient variants in Kano North-West Nigeria

Main Article Content

Jelani, I Abdullahi, HL Alhassan, AJ Dalhatu, MM Dangambo, MA Abacha, FZ Haruna, S Mahmud, RI Yandutse, MI Hamza, HD Abdu, R Musa, A. H

Abstract

Studies from sub-Saharan Africa where malaria is endemic have observed high incidences of Glucose-6-phosphate dehydrogenase A- (G-6-PD A-) deficiency that sporadically leads to manifest haemolytic anaemia. The severity of this disease depends on the genetic variant involved, thus, pinpointing the type of G-6-PD variants will help in the management of G-6-PD deficiency. This is not exactly known among Hausa and Fulani ethnics in Northern Nigeria, hence the need for the study. Two ml of venous blood samples were collected from twenty (20) G-6-PD deficient individuals and dispensed into EDTA bottle to study the coding region of G-6-PD gene by using PCR-Sequencing techniques. Sequencing of the G-6-PD-deficient samples revealed two major polymorphic variants; A376G substitution (exon-5: Asn126Asp) and A376G/G202A substitution (exon-4: Val68Met) commonly observed among Hausa and Fulani ethnics. This is the first study of G-6-PD mutations in Kano, North-west Nigeria. The G-6-PD deficiency in Hausa and Fulani ethnics were associated with African variants (202A/376G G6PD A- allele) in exon 4 and no mutation was found within exon 6-7.

Article Details

How to Cite
I, Jelani, et al. Molecular Characterization of Glucose-6-Phosphate Dehydrogenase deficient variants in Kano North-West Nigeria. Medical Research Archives, [S.l.], v. 12, n. 7, july 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5312>. Date accessed: 21 dec. 2024. doi: https://doi.org/10.18103/mra.v12i7.5312.
Section
Research Articles

References

1. Mason PJ, Bautista JM, Gilsanz F. G-6-PD deficiency: the genotype- phenotype association. Blood Reviews, 2007; 21: 267-283.

2. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. The Lancet, 2008; 371: 64-74.

3. Chen EY, Cheng A, Lee A, Kuang WJ, Hillier L, Green P, Schlessinger D, Ciccodicola A, D’Urso M. Sequence of human glucose-6-phosphate dehydrogenase cloned in plasmids and a yeast artificial chromosome. Genomics, 1991; 10(3): 792-800.

4. Mason, P. J., Sonati, M. F., MacDonald, D., Lanza, C., Busutil, D., Town, M., Corcoran, C.M., Kaeda, J. S., Stevens, D. J., Al-Ismail, S., Altay, C., Hatton, D. S., Lewis, D. S., McMullin, M. F., Meloni, T., Paul, B., Pippard, M., Prentice, A. G. T., Vulliamy, T. J. and Luzzatto, L. (1995). New glucose-6- phosphate dehydrogenase mutations associated with chronic anaemia. Blood, 85: 1377-1380.

5. Jummanah J, Biochemical Estimation of Glucose 6 Phosphate Dehydrogenase Deficiency in Saudi Adults: Different Methods and Its Rationalization. Advances in Bioscience and Biotechnology, 2014; 5:435-437

6. Mehta A, Mason PJ, Vulliamy TJ. Glucose-6-phosphate dehydrogenase deficiency. Best Practice and Research Clinical Haematology. 2000; 13(1): 21-38.

7. Luzzatto, L. Glucose 6-phosphate dehydrogenase deficiency: From genotype to phenotype. Haematologica, 2006; 91(10): 1303-1306.

8. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis. Blood Cells Mol Dis. 2009; 42:267–278.

9. Kwok CJ, Martin ACR, Au, WNS, Lam VM.S. G6PDdb, an integrated database of glucose-6-phosphate dehydrogenase (G6PD) mutations, Human Mutation, 2002; 19(3):217-224.

10. Minucci A, Giardina B, Zuppi C, Capoluongo E. Glucose-6-phosphate dehydrogenase laboratory assay: How, when, and why? IUBMB Life. 2009; 61:27–34.

11. Minucci A, Moradkhani K, Hwang M, Zuppi C, Giardina B, Capoluongo P. Glucose-6-phosphate dehydrogenase (G-6-PD) mutations database: Review of the “old” and update of the new mutations. Blood Cells Molecular Disease, 2012; 48:154–165.

12. Ramírez-Nava EJ, Ortega-Cuellar D, Serrano-Posada H, González-Valdez A, Vanoye-Carlo A, Hernández-Ochoa B, Sierra-Palacios E, Hernández-Pineda J, Rodríguez-Bustamante E, Arreguin-Espinosa R, Oria-Hernández J, Reyes-Vivas H, Marcial-Quino J, Gómez-Manzo S. Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant. International Journal of Molecular Sciences, 2017; 18 (2244): 1-18.

13. Scriver C. Glucose-6-Phosphate Dehydrogenase Deficiency, 7th edn, McGraw Hill: New York, 1995.

14. Clark TG, Fry AE, Auburn S, Campino S, Diakite M, et al. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility. European Journal of Human Genetics, 2009; 17:1080–1085.

15. Tishkoff SA, Varkonyi R, Cahinhinan N et al: Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science, 2001; 293: 455–462.

16. De-Araujo C, Migot-Nabias F, Guitard J, Pelleau S, Vulliamy T, Ducrocq R. The role of the G6PD A– 376G/968C allele in glucose-6-phosphate dehydrogenase deficiency in the seerer population of Senegal. Haematologica/ the Hematology Journal, 2006; 91(2): 262-263.

17. Beutler E, Kuhl W, Vives-Corrons JL, Prchal JT: Molecular heterogeneity of glucose-6-phosphate dehydrogenase A. Blood 1989; 74: 2550–2555.

18. Ruwende C, Khoo SC, Snow RW, Yates SNR, Kwiatkowski D, Gupta S, Warn P, Allsopp CEM, Gilbert SC, Peschu N, Newbold CI, Greenwood BM, Marsh K. and Hill, A. V. S. (1995). Natural selection of hemi and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature, 1995;376: 246– 249.

19. Guindo A, Fairhurst RM, Doumbo OK, Wellems TE, Diallo DA: X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med 2007; 4:e66.

20. Duflo B, Diallo A, Toure K, Soula G. Glucose-6-phosphate dehydrogenase deficiency in Mali. Epidemiology and pathological aspects, Bull Soc Pathol Exot Filiales, 1979; 72(3):258-64.

21. Bouanga J C, Mouélé R, Préhu C, Wajcman H, Feingold J, Galactéros F. Glucose-6-phosphate dehydrogenase deficiency and homozygous sickle cell disease in Congo, Humal Heredity (1998) 48 (4): 192–197.

22. Davis JC, Clark TD, Kemble SK, Talemwa N, Njama-Meya D, et al. Longitudinal study of urban malaria in a cohort of Ugandan children: description of study site, census and recruitment. Malaria Journal. 2006; 5:18.

23. Mombo LE, Ntoumi F, Bisseye C, Ossari S, Lu CY, Nagel RL, Krishnamoorthy R. Human genetic polymorphisms and asymptomatic plasmodium falciparum malaria in Gabonese school children. American Journal of Tropical Medicine and Hygiene, 2003; 68: 186-190.

24. F. Migot-Nabias, L. E. Mombo, A. J. F. Luty et al., “Human genetic factors related to susceptibility to mild malaria in Gabon,” Genes and Immunity, 2000; 1(7): 435–441.

25. Vaca G, Arámbula E, Monsalvo A, Medina C, Nuñez C, Sandoval L, López-Guido B, Glucose-6-phosphate dehydrogenase (G-6-PD) mutations in Mexico: four new G-6-PD variants. Blood Cells, Molecules, and Diseases, 2003; 31(1): 112-120.

26. Kotea R, Kaeda JS, Yan SL, Sem-Fa N, Beesoon S, Jankee S, Ramasawmy R, Vuilliamy T, Bradnock RW, Bautista J, Luzzatto L, Khrishnamoorthy R, Mason PJ. Three major G-6-PD-deficient polymorphic variants identified among the Mauritian population. British Journal of Haematology, 1999; 104: 849–854.

27. LaRue N, Kahn M, Murray M, Leader BT, Bansil P, McGray S, Kalnoky M, Zhang H, Huang H, Jiang H, Domingo GJ. Comparison of Quantitative and Qualitative Tests for Glucose-6-Phosphate Dehydrogenase Deficiency. The American Society of Tropical Medicine and Hygiene, 2014; 91(4): 854–861.

28. Assefa A, Ali A, Deressa W, Tsegaye W, Abebe G, Sime H, Kebede A, Jima D, Kassa M, Abreha T, Teka H, Solomon H, Malone J, Shi Y, Zhou Z, Reithinger R, Hwang J. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide study Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide study. Malaria Journal, 2018; 17(388): 1-7.

29. Farouk ZL, Ibrahim M, Ogala WN, Glucose-6-phosphate dehydrogenase deficiency; the single most important cause of neonatal hyperbilirubinaemia in Kano, Nigeria. Nigerian Journal of Paediatrics, 2017; 44 (2): 44–49.

30. Gilles HM, Fletcher KA, Hendrickse RG, Lindner R, Reddy S, Allan N. Glucose-6-phosphate-dehydrogenase deficiency, sickling, and malaria in African children in South Western Nigeria. Lancet. 1967; 21;1(7482):138–140.

31. Luzzatto, L. and Allan, N C. (1968). Relationship between the genes for glucose-6-phosphate dehydrogenase and for haemoglobin in a Nigerian population, Nature, 219(5158):1041-1042.

32. Bienzle, U., Ayeni, O., Lucas, A.O., Luzzatto, L. (1972). Glucose-6-phosphate dehydrogenase and malaria. Greater resistance of females heterozygous for enzyme deficiency and of males with non-deficient variant. Lancet, 1: 107–110.

33. Martini, G., Toniolo, D., Vulliamy, T., Luzzatto, L., Dono, R., Viglietto, G., Paonessa, GG., D'Urso, M. and Persico, M. G. (1986). Structural analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase. European Molecular Biology Organization, Journal, 5(8):1849-55.

34. Ademowo, O. G., Falusi, A. G. and Mewoyeka, O. O. (1995). Prevalence of asymptomatic parasitaemia in an urban and rural community in south western Nigeria. Central African Journal of Medicine, 41(1): 18-21.

35. May, J., Meyer, C. G., Grossterlinden, L., Ademowo, O. G., Mockenhaupt, F. P., Olumese, P. E., Falusi, A. G., Luzatto, L. and Bienzie, U. (2000). Red cell glucose-6-phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian population. Tropical Medicine and International Health, 5(2): 119-123.

36. Ademowo, O. G. and Falusi, A. G. (2002). Molecular epidemiology and activity of erythrocyte G-6-PD variants in a homogeneous Nigerian population. East African Medical Journal, 79(1): 42-44.

37. Meissner PE, Coulibaly B, Mandi G, Mansmann U, Witte S, Schiek W, Muller O, Heiner-Schirmer R, Mockenhaupt FP, Bienzle U.. Diagnosis of red cell G-6-PD deficiency in rural Burkina Faso: comparison of a rapid fluorescent enzyme test on filter paper with polymerase chain reaction based genotyping, British Journal of Haematology, 2005; 131: 395-399.

38. Ouattara AK, Yameogo P, Diarra B, Obiri-Yeboah D, Yonli A, Compaore TR, Soubeiga ST, Djigma FW, Simpore J. Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Burkina Faso: g-6-pd betica selma and santamaria in people with symptomatic malaria in ouagadougou. Mediterranean Journal of Hematology and Infectious Diseases, 2016; 8(1): 1-8.

39. Gampio-Gueye NS, Peko SM, Nderu D, Koukouikila‑Koussounda F, Vouvoungui C, Kobawila SC, Velavan TP, Ntoumi F. An update on glucose‑6‑phosphate dehydrogenase deficiency in children from Brazzaville, Republic of Congo. Malaria Journal, 2019; 18(57): 2-6.

40. Lin M, Yang LY, Xie DD, Chen JT, Nguba Sm M, Ehapo CS, Xiao FZ, Juan UME, Rocio AM, Maximo MOO, Hui Y, Hui TY, Ji DC. G6PD Deficiency and Hemoglobinopathies: Molecular Epidemiological Characteristics and Healthy Effects on Malaria Endemic Bioko Island, Equatorial Guinea. The Public Library of Science ONE, 2015; 10(4): 1-10.

41. Lo E, Zhong D, Raya B, Pestana K, Koepfli C, Lee M, Yewhalaw D, Yan G. Prevalence and distribution of G-6-PD deficiency: Implication for the use of primaquine in malaria treatment in Ethiopia. Malaria Journal, 2019; 18(340): 1-10.

42. Burchard GD, Browne ENL, Sievertsen J, May J, Meyer CG. Spleen size determined by ultrasound in patients with sickle cell trait, HbAC trait and glucose-6-phosphatedehydrogenase deficiency in a malaria hyper endemic area (Ashanti Region, Ghana). Acta Tropica, 2001; 80: 103-109.

43. Maiga B, Dolo A, Campino S, Sepulveda N, Corran P, Rockett KA, Troye-Blomberg M, Doumbo OK, Clark TG. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali. Malaria Journal, 2014; 13(270):1-12.

44. Djigo OKM, Bollahi MA, Hasni-Ebou M, Salem MSOA, Tahar R, Bogreau H, Basco L, Boukhary AOMS. Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania. The Public Library of Science, 2019; 14(9): 1-11.

45. Daniel HH, Alex I, Ruth N, Grace A, Toini H, Larysa A, Jane M, Petrina U, Jeffrey MP, Beatrice G, Isaac KQ. Glucose-6-phosphate dehydrogenase deficiency genotypes and allele frequencies in the Kavango and Zambezi regions of northern Namibia. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2019; 113 (8): 483–488.

46. Enevold A, Vestergaard LS, Lusingu J, Drakeley CJ, Lemnge MM, Theander TG, Bygbjerg IC, Alifrangis M. Rapid screening for glucose-6-phosphate dehydrogenase deficiency and haemoglobin polymorphisms in Africa by a simple high-throughput SSOP-ELISA method. Malaria Journal, 2005; 4(61): 1-8.

47. Manjurano A, Sepulveda N, Nadjm B, Mtove G, Wangai H, Maxwell C, Olomi R, Reyburn H, Riley EM, Drakeley CJ, Clark TG, Consortium M. African Glucose-6-Phosphate Dehydrogenase Alleles Associated with Protection from Severe Malaria in Heterozygous Females in Tanzania. Public Library of Science ONE Genetics 2015; 11(2):e1004960.

48. Vizzi E, Bastidas G, Hidalgo M, Colman L, Pérez HA. Prevalence and molecular characterization of G6PD deficiency in two Plasmodium vivax endemic areas in Venezuela: predominance of the African A‑202A/376G variant. Malaria Journal, 2016; 15(19):1-9.

49. Pereira LL, Bravin CA, Cintra TS, Cassa WS, Santos TA, Fonseca A, Pratte-Santos R Prevalence of G6PD deficiency and molecular characterization of G202A, A376G and C563T polymorphisms in newborns in Southeastern Brazil. einstein (São Paulo). 2019; 17(1): 1-7.

50. Zamorano-Jimenez CA, Baptista-Gonzalez HA, Bouchan-Valencia P, Granados-Cepeda ML, Trueba-Gomez R, Coeto-Borona G, Rosenfeld-Mann F, Rosa-Mireles LB, Melendez-Ramirez R. Molecular Identification of glucose-6-phosphate dehydrogenase (G6PD) detected in neonatal screening. Gaceta Medico de Mexico, 2015; 151: 31-37.

51. Badens C, Martinez di Montemuros F, Thuret I, Michel G, Mattei JF, Cappellini MD, Lena-Russo D. Molecular basis of haemoglobinopathies and G-6-PD deficiency in the Comorian population. Haematology Journal, 2000; 1: 264-268.

52. Di-montemuros FM, Dotti C, Tavazzi D, Fiorelli G, Cappellini MD. Molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) Variants in Italy. Haematologica, 1997; 82: 440-445.

53. Benmansour I, Moradkhani K, Moumn I, Wajcman H, Hafsia R, Ghanem A, Abbes S, Prehu C. Two New Class III G6PD Variants [G6PD Tunis (c.920A>C: p.307Gln>Pro) and G6PD Nefza (c.968T>C: p.323 Leu>Pro)] and Overview of the Spectrum of Mutations in Tunisia. Blood Cells Molecules and Disease, 2013; 50(2): 110-114.