Association between G6PD G202A Polymorphism and HbA1c among Patients with Type II Diabetes in Nigeria
Keywords:
T2D, G6PD, G202A, HbA1cAbstract
Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. In hyperglycemic cases, haemoglobin binds irreversibly with glucose to form glycated haemoglobin (HbA1c) an accepted diagnostic test for type 2 diabetes mellitus (T2DM) used for monitoring glycaemic control in patients with diabetes. Some genetic variants influence the characteristics of HbA1c, via the erythrocytic pathway (erythrocytic variants), while some act through the glycemic pathway (glycemic variants). Glycemic variants increase the risk of developing diabetes, while erythrocytic variants have no association with the risk of diabetes. G202A, a variant of G6PD, is a single nucleotide polymorphism (SNP) associated with HbA1c in non-diabetic African Americans. G202A variant lowers HbA1c levels irrespective of an individual’s blood glucose level. Alterations in HbA1c caused by a G202A SNP of the G6PD in normal African Americans leads to a massive under-diagnosis of T2DM. There is no previous study on the effect of this SNP on HbA1c in diabetic individuals hence the need for this study. Methods: Thirty-two non-diabetic and 54 diabetic male adult subjects were recruited after signing informed consent. Venous blood was collected from which fasting blood glucose and glycated haemoglobin were measured. DNA was extracted from whole blood. The samples were amplified, and amplicons digested using the PCR-RFLP technique and were visualised using a UV transilluminator. Data were analyzed using SPSS version 20 and SHEsis online software. Results: The genotypic distributions of G6PD G202A in the diabetic group were statistically significant (HWE p˂0.05). The minor allele frequency 202A was 20% and 16% in diabetics and non-diabetics, respectively. G6PD G202A polymorphism was associated with HbA1c in diabetic subjects. G6PD G202A SNP showed association with diabetes (p-value=0.003) and HbA1c in diabetic subjects. Conclusion: There is an association between HbA1c and G6PD G202A SNP in diabetic subjects.
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References
American Diabetes Association, 2015. 2. Classification and diagnosis of diabetes. Diabetes care, 38(Supplement 1), pp.S8-S16.
Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, 1000 Genomes Project Consortium, 2015. A global reference for human genetic variation. Nature, 526(7571), p.68.
Babalola, M.O., Imaga, N.A., Samuel, T.A., Diriwari, I.P., Kolade, O., Ezeamalu, I., Laoye, A.O. and Ojewunmi, O.O., 2018. Genetic Polymorphisms of Glucose-6-Phosphate Dehydrogenase in Lagos, Nigeria. Hemoglobin, 42(1), pp.47-50.
Battistuzzi, G., Esan, G.J., Fasuan, F.A., Modiano, G. and Luzzatto, L., 1977. Comparison of GdA and GdB activities in Nigerians. A study of the variation of the G6PD activity. American journal of human genetics, 29(1), p.31.
Bry, L., Chen, P.C. and Sacks, D.B., 2001. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clinical chemistry, 47(2), pp.153-163.
Chen, P., Ong, R.T.H., Tay, W.T., Sim, X., Ali, M., Xu, H., Suo, C., Liu, J., Chia, K.S., Vithana, E. and Young, T.L., 2013. A Study Assessing the Association of Glycated Hemoglobin A 1C (HbA 1C) Associated Variants with HbA 1C, Chronic Kidney Disease and Diabetic Retinopathy in Populations of Asian Ancestry. PloS one, 8(11), p.e79767.
Chen, Z., Tang, H., Qayyum, R., Schick, U.M., Nalls, M.A., Handsaker, R., Li, J., Lu, Y., Yanek, L.R., Keating, B. and Meng, Y., 2013. Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network. Human molecular genetics, 22(12), pp.2529-2538.
Clark, T.G., Fry, A.E., Auburn, S., Campino, S., Diakite, M., Green, A., Richardson, A., Teo, Y.Y., Small, K., Wilson, J. and Jallow, M., 2009. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility. European Journal of Human Genetics, 17(8), pp.1080-1085.
Ding, K., de Andrade, M., Manolio, T.A., Crawford, D.C., Rasmussen-Torvik, L.J., Ritchie, M.D., Denny, J.C., Masys, D.R., Jouni, H., Pachecho, J.A. and Kho, A.N., 2013. Genetic variants that confer resistance to malaria are associated with red blood cell traits in African-Americans: an electronic medical record-based genome-wide association study. G3: Genes, Genomes, Genetics, 3(7), pp.1061-1068.
Dolo, A., Maiga, B., Guindo, A., Diakité, S.A., Diakite, M., Tapily, A., Traoré, M., Sangaré, B., Arama, C., Daou, M. and Doumbo, O., 2014. Frequency of glucose-6-phosphate dehydrogenase deficiency (A-376/202) in three Malian ethnic groups. Bulletin de la Societe de pathologie exotique (1990), 107(3), pp.165-170.
Howes, R.E., Piel, F.B., Patil, A.P., Nyangiri, O.A., Gething, P.W., Dewi, M., Hogg, M.M., Battle, K.E., Padilla, C.D., Baird, J.K. and Hay, S.I., 2012. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med, 9(11), p.e1001339.
Jain, V., Shivkumar, S. and Gupta, O., 2014. Health-related quality of life (hr-qol) in patients with type 2 diabetes mellitus. North American journal of medical sciences, 6(2), p.96.
Leong, A. and Wheeler, E., 2018. Genetics of HbA1c: a case study in clinical translation. Current opinion in genetics & development, 50, pp.79-85.
Maiga, B., Dolo, A., Campino, S., Sepulveda, N., Corran, P., Rockett, K.A., Troye-Blomberg, M., Doumbo, O.K. and Clark, T.G., 2014. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali. Malaria journal, 13(1), pp.1-12.
Manjurano, A., Sepúlveda, N., Nadjm, B., Mtove, G., Wangai, H., Maxwell, C., Olomi, R., Reyburn, H., Drakeley, C.J., Riley, E.M. and Clark, T.G., 2015. USP38, FREM3, SDC1, DDC, and LOC727982 gene polymorphisms and differential susceptibility to severe malaria in Tanzania. The Journal of infectious diseases, 212(7), pp.1129-1139.
Mathias, R.A., Deepa, M., Deepa, R., Wilson, A.F. and Mohan, V., 2009. Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India. Metabolism, 58(10), pp.1439-1445.
Mortensen, H.B. and Christophersen, C., 1983. Glucosylation of human haemoglobin a in red blood cells studied in vitro. Kinetics of the formation and dissociation of haemoglobin A1c. Clinica chimica acta, 134(3), pp.317-326.
Paterson, A.D., 2017. HbA1c for type 2 diabetes diagnosis in Africans and African Americans: Personalized medicine NOW!. PLoS medicine, 14(9), p.e1002384.
Saltiel, A.R. and Kahn, C.R., 2001. Insulin signalling and the regulation of glucose and lipid metabolism. Nature, 414(6865), pp.799-806.
Selvin, E., Steffes, M.W., Zhu, H., Matsushita, K., Wagenknecht, L., Pankow, J., Coresh, J. and Brancati, F.L., 2010. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. New England Journal of Medicine, 362(9), pp.800-811.
Simonis-Bik, A.M., Eekhoff, E.M., Diamant, M., Boomsma, D.I., Heine, R.J., Dekker, J.M., Willemsen, G., Van Leeuwen, M. and De Geus, E.J., 2008. The heritability of HbA1c and fasting blood glucose in different measurement settings. Twin Research and Human Genetics, 11(6), pp.597-602.
Singh, N.A., Clements, K.M. and Singh, M.A.F., 2001. The efficacy of exercise as a long-term antidepressant in elderly subjects: a randomized, controlled trial. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 56(8), pp.M497-M504.
Snieder, H., Sawtell, P.A., Ross, L., Walker, J., Spector, T.D. and Leslie, R.D.G., 2001. HbA1c levels are genetically determined even in type 1 diabetes: evidence from healthy and diabetic twins. Diabetes, 50(12), pp.2858-2863.
Tishkoff, S.A., Varkonyi, R., Cahinhinan, N., Abbes, S., Argyropoulos, G., Destro-Bisol, G., Drousiotou, A., Dangerfield, B., Lefranc, G., Loiselet, J. and Piro, A., 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science, 293(5529), pp.455-462.
Venkataraman, K., Kao, S.L., Thai, A.C., Salim, A., Lee, J.J.M., Heng, D., Tai, E.S. and Khoo, E.Y.H., 2012. Ethnicity modifies the relation between fasting plasma glucose and HbA1c in Indians, Malays and Chinese. Diabetic medicine, 29(7), pp.911-917.
Wheeler, E., Leong, A., Liu, C.T., Hivert, M.F., Strawbridge, R.J., Podmore, C., Li, M., Yao, J., Sim, X., Hong, J. and Chu, A.Y., 2017. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis. PLoS medicine, 14(9), p.e1002383.
World Health Organization, 2018. Global Report on Diabetes http://www. who. int/diabetes/global-report/en/. Published April, 2016. Accessed June, 11.
World Health Organization, 2011. Use of glycated haemoglobin (HbA1c) in diagnosis of diabetes mellitus: abbreviated report of a WHO consultation (No. WHO/NMH/CHP/CPM/11.1). World Health Organization.
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