Genetic Predisposition for Type 2 Diabetes Mellitus in a Cameroonian Population: Contribution of rs4731702 (C/T) Polymorphism of Krüppel-Like Factor 14 Gene
Introduction: Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. Patients and Methods: This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. Conclusion: This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.
References
[1]
Guillausseau, P.J., Meas, T., Virally, M., Laloi-Michelin, M., Médeau, V. and Kevorkian, J.P. (2008) Abnormalities in Insulin Secretion in Type 2 Diabetes mellitus. Diabetes & Metabolism, 34, S43-S48. https://doi.org/10.1016/S1262-3636(08)73394-9
[2]
International Diabetes Federation (2019) IDF Diabetes Atlas. 9th Edition, International Diabetes Federation, Brussels. http://www.idf.org/diabetesatlas
[3]
McCarthy, M.I. (2010) Genomics, Type 2 Diabetes, and Obesity. New England Journal of Medicine, 363, 2339-2350. https://doi.org/10.1056/NEJMra0906948
[4]
Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., et al. (2007) A Genome-Wide Association Study Identifies Novel Risk Loci for Type 2 Diabetes. Nature, 445, 881-885. https://doi.org/10.1038/nature05616
[5]
Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University and Novartis Institutes of BioMedical Research (2007) Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels. Science, 316, 1331-1336. https://doi.org/10.1126/science.1142358
[6]
Wellcome Trust Case Control Consortium (2007) Genome-Wide Association Study of 14,000 Cases of Seven Common Diseases and 3,000 Shared Controls. Nature, 447, 661-678. https://doi.org/10.1038/nature05911
[7]
McCarthy, M.I. and Zeggini, E. (2009) Genome-Wide Association Studies in Type 2 Diabetes. Current Diabetes Reports, 9, 164-171. https://doi.org/10.1007/s11892-009-0027-4
[8]
Lu, S., Xie, Y., Lin, K., Li, S., Zhou, Y., Ma, P., Lu, Z. and Zhou, X. (2012) Genome-Wide Association Studies-Derived Susceptibility Loci in Type 2 Diabetes: Confirmation in a Chinese Population. Clinical and Investigative Medicine, 35, E327-E333. https://doi.org/10.25011/cim.v35i5.18706
[9]
Imamura, M., Takahashi, A., Yamauchi, T., Hara, K., Yasuda, K., Grarup, N., et al. (2016) Genome-Wide Association Studies in the Japanese Population Identify Seven Novel Loci for Type 2 Diabetes. Nature Communication, 7, Article No. 10531. https://doi.org/10.1038/ncomms10531
[10]
Rotimi, C.N., Chen, G., Adeyemo, A.A., Furbert-Harris, P., Parish-Gause, D., Zhou, J., Berg, K., et al. (2004) Africa America Diabetes Mellitus (AADM) Study. A Genome-Wide Search for Type 2 Diabetes Susceptibility Genes in West Africans: The Africa America Diabetes Mellitus (AADM) Study. Diabetes, 53, 838-841. https://doi.org/10.2337/diabetes.53.3.838
[11]
Chen, G., Adeyemo, A., Zhou, J., Chen, Y., Huang, H., Doumatey, A., et al. (2007) Genome-Wide Search for Susceptibility Genes to Type 2 Diabetes in West Africans: Potential Role of C-Peptide. Diabetes Research and Clinical Practice, 78, e1-e6. https://doi.org/10.1016/j.diabres.2007.04.010
[12]
Yako, Y.Y., Guewo-Fokeng, M., Balti, E.V., Bouatia-Naji, N., Matsha, T.E., Sobngwi, E., et al. (2016) Genetic Risk of Type 2 Diabetes in Populations of the African Continent: A Systematic Review and Meta-Analyses. Diabetes Research and Clinical Practice, 114, 136-150. https://doi.org/10.1016/j.diabres.2016.01.003
[13]
Parker-Katiraee, L., Carson, A.R., Yamada, T., Arnaud, P., Feil, R., Abu-Amero, S.N., et al. (2007) Identification of the Imprinted KLF14 Transcription Factor Undergoing Human-Specific Accelerated Evolution. PLoS Genetics, 3, e65. https://doi.org/10.1371/journal.pgen.0030065
[14]
Kerrin, S.S., Asa, K.H., Grundberg, E., Nica, A.C., Thorleifsson, G., Kong, A., et al. (2011) Identification of an Imprinted Master Trans Regulator at the KLF14 Locus Related to Multiple Metabolic Phenotypes. Nature Genetic, 43, 561-564. https://doi.org/10.1038/ng.833
[15]
Dang, D.T., Pevsner, J. and Yang, V.W. (2000) The Biology of the Mammalian Kruppel-Like Family of Transcription Factors. The International Journal of Biochemistry & Cell Biology, 32, 1103-1121. https://doi.org/10.1016/S1357-2725(00)00059-5
[16]
Pearson, R., Fleetwood, J., Eaton, S., Crossley, M. and Bao, S. (2008) Kruppel-Like Transcription Factors: A Functional Family. The International Journal of Biochemistry & Cell Biology, 40, 1996-2001. https://doi.org/10.1016/j.biocel.2007.07.018
[17]
Mato-Mofo, E.P., Fosso, P.P., Atogho-Tiedeu, B., Noubiap, J.J., Evehe, M.S., Djokam-Dadjeu, R., et al. (2016) The Pro12Ala Polymorphism in the PPAR-γ2 Gene Is Not Associated to Obesity and Type 2 Diabetes in a Cameroonian Population. Journal of BMC Obesity, 3, Article No. 26. https://doi.org/10.1186/s40608-016-0104-6
[18]
Nanfa, D., Sobngwi, E., Atogho-Tiedeu B., Noubiap, J.J., Donfack, O.S., Mofo, E.P., et al. (2015) Association between the TCF7L2 rs12255372(G/T) Gene Polymorphism and Type 2 Diabetes Mellitus in a Cameroonian Population: A Pilot Study. Clinical and Translational Medicine, 4, e17. https://doi.org/10.1186/s40169-015-0058-1
[19]
Guewo-Fokeng, M., Sobngwi, E., Atogho-Tiedeu, B., Donfack, O.S., Noubiap, J.J., Ngwa, E.N., et al. (2015) Contribution of the TCF7L2 rs7903146(C/T) Gene Polymorphism to the Susceptibility to Type 2 Diabetes Mellitus in Cameroon. Journal of Diabetes & Metabolic Disorders, 14, Article No. 26. https://doi.org/10.1186/s40200-015-0148-z
[20]
American Diabetes Association (2012) Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 35, S64-S71. https://doi.org/10.2337/dc12-s064
[21]
World Health Organization (2006) Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia. World Health Organization, Geneva.
[22]
Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F. and Turner, R.C. (1985) Homeostasis Model Assessment: Insulin Resistance and Beta-Cell Function from Fasting Plasma Glucose and Insulin Concentrations in Man. Diabetologia, 28, 412-419. https://doi.org/10.1007/BF00280883
[23]
Guillen, M.A., Mejia, F.A., Villena, J., Turin, C.G., Carcamo, C.P. and Ticse, R. (2015) Insulin Resistance by Homeostasis Model Assessment in HIV-Infected Patients on Highly Active Antiretroviral Therapy: Cross-Sectional Study. Diabetology & Metabolic Syndrome, 7, Article No. 49. https://doi.org/10.1186/s13098-015-0046-z
[24]
Plowe, C.V., Djimde, A., Bouare, M., Doumbo, O. and Wellems T. (1995) Pyrimethamine and Proguanil Resistance-Conferring Mutations in Plasmodium falciparum Dihydrofolate Reductase: Polymerase Chain Reaction Methods for Surveillance in Africa. American Journal of Tropical Medicine and Hygiene, 52, 565-568. https://doi.org/10.4269/ajtmh.1995.52.565
[25]
Allain, C.C., Poon, L.S., Chan, C.S., Richmond, W. and Fu P.C. (1974) Enzymatic Determination of Serum Total Cholesterol. Clinical Chemistry, 20, 470-475. https://doi.org/10.1093/clinchem/20.4.470
[26]
Bucolo G. and David H. (1973) Quantitative Determination of Serum Triglycerides by Use of Enzymes. Clinical Chemistry, 19, 476-482. https://doi.org/10.1093/clinchem/19.5.476
[27]
Burstein, M., Scholnick, H.R. and Morfin R. (1970) Rapid Method for the Isolation of Lipoproteins from Human Serum by Precipitation with Polyanions. Journal of Lipid Research, 11, 583-595. https://doi.org/10.1016/S0022-2275(20)42943-8
[28]
Friedewald, W.T., Levy, R.I. and Fredrickson D.S. (1972) Estimation of Low Density Lipoprotein Cholesterol without the Use of the Preparative Ultracentrifuge. Clinical Chemistry, 18, 499-502. https://doi.org/10.1093/clinchem/18.6.499
[29]
Expert Panel (2001) Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 285, 2486-2497. https://doi.org/10.1001/jama.285.19.2486
[30]
Gauderman, W.J. and Morrison, J.M. (2006) Quanto: A Computer Program for Power and Sample Size Calculations for Genetic-Epidemiology Studies. https://www.scienceopen.com/document?vid=2944f68a-3b3d-4e86-90a3-3d3c1fab3ffa
[31]
Kong, A., Steinthorsdottir, V., Masson, G., Thorleifsson, G., Sulem, P., Besenbacher, S., et al. (2009) Parental Origin of Sequence Variants Associated with Complex Diseases. Nature, 462, 868-874. https://doi.org/10.1038/nature08625
[32]
Huang, P., Yin, R.X., Huang, K.K., Zeng, X.N., Guo, T., Lin, Q.Z., Wu, J., Wu, D.F. and Li, H. and Pan, S.L. (2013) Association of the KLF14 rs4731702 SNP and Serum Lipid Levels in the Guangxi Mulao and Han Populations. BioMed Research International, 2013, Article ID: 231515. https://doi.org/10.1155/2013/231515
[33]
Tiedeu, B.A., Guewo-Fokeng, M., Lontchi-Yimagou, E., Mbanya, J.C., Sobngwi, E. and Mbacham, F.W. (2017) Association of rs4731702(C/T) Polymorphism of Krüppel Like Factor 14 (KLF14) Gene with Ketosis-Prone Diabetes (KPD) in a Cameroonian Population. Journal of Global Diabetes & Clinical Metabolism, 2, Article No. 021.
[34]
Gao, K., Wang, J., Li, L., Zhai, Y., Ren, Y., You, H., Wang, B., et al. (2016) Polymorphisms in Four Genes (KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963) and Their Correlation with Type 2 Diabetes Mellitus in Han Chinese in Henan Province, China. International Journal of Environmental Research and Public Health, 13, Article No. 260. https://doi.org/10.3390/ijerph13030260
[35]
Elston, R.C. and Forthofer, R. (1977) Testing for Hardy-Weinberg Equilibrium in Small Samples. Biometrics, 33, 536-542. https://doi.org/10.2307/2529370
