IGF2 ApaI A/G Polymorphism Evaluated in ESRD Individuals as a Biomarker to Identify Patients with New Onset Diabetes Mellitus after Renal Transplant in Asian Indians
- 1 Department of Genetics and Molecular Medicine, Kamineni Hospital, Hyderabad, India
- 2 Department of Genetics and Molecular Medicine, Kamineni Hospital, Hyderabad, India
- 3 Center of Medical Genetics, Sir Ganga Ram Hospitals, New Delhi, India
- 4 Department of Nephrology, Kamineni Hospital, Hyderabad, India
- 5 Department of Genetics and Molecular Medicine, Kamineni Hospital, Hyderabad, India
- 6 Department of Biochemistry, Kasturba Medical College, Manipal University, Manipal, India
- 7 Department of Genetics and Molecular Medicine, Kamineni Hospital, Hyderabad, India
- 8 Department of Genetics and Molecular Medicine, Kamineni Hospital, Hyderabad, India
Abstract
Insulin like growth factors2 (IGF2) regulates pancreatic β -cell renewal and apoptosis, which in turn plays a role in altering insulin activity and glucose homeostasis. Polymorphisms in IGF2 gene have been associated with altered levels of IGF2. Hence, ApaI polymorphism in exon 9 of IGF2 (rs#680) gene was assessed in patients with end stage renal disease (ESRD) to identify individuals at risk of developing new onset diabetes mellitus (NODM) in Asian Indians. Isolated DNA was used for PCR&RFLP based genotyping of IGF2 ApaI polymorphism which was carried out in 364 individuals these included 140 patients who had undergone renal transplant, 42 of which developed new onset diabetes mellitus after renal transplant and 224 healthy control volunteers. In the present study NODM or post transplant diabetes mellitus (PTDM) showed a significant association with G allele and AG genotype when compared with the Non- NODM ESRD patients after transplant (OR 2.081, 95% CI = 1.191 - 3.634, p = 0.01 and OR 3.188, 95% CI = 1.498 - 6.785, p = 0.002) ESRD patients with healthy controls also showed an association with G allele and AG genotype (OR 1.512, 95% CI = 1.060 - 2.155, p = 0.02 and OR 2.235, 95% CI = 1.453 - 3.438, p = 0.0002). IGF2 could be used as a biomarker to identify individuals at high risk of developing NODM , it would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals undergoing transplant. Present study shows the importance of IGF2 ApaI polymorphism in assessing the risk of NODM in ESRD individuals in Asian Indians with ESRD.
- L. M. Hart, A. Fritsche, I. Rietveld, J. M. Dekker, G. Nijpels, F. Machicao, M. Stumvoll, C. M. van Duijn, H. U. Häring, R. J. Heine, J. A. Maassen and T. W. van Haeften, “Genetic Factors and Insulin Secretion. Gene Variants in the IGF Genes,” Diabetes, Vol. 53, Suppl. 1, 2004, pp. 26-30. doi:10.2337/diabetes.53.2007.S26
- J. J. Kim and D. Accili, “Signalling through IGF-I and Insulin Receptors: Where Is the Specificity?” Growth Hormone and IGF Research, Vol. 12, No. 2, 2002, pp. 84-90. doi:10.1054/ghir.2002.0265
- C. N. Hales and D. J. Barker, “The Thrifty Phenotype Hypothesis,” British Medical Bulletin, Vol. 60, No. 1, 2001, pp. 5-20. doi:10.1093/bmb/60.1.5
- M. S. Sandhu, J. M. Gibson, A. H. Heald, D. B. Dunger and N. J. Wareham, “Low Circulating IGF-II Concentrations Predict Weight Gain and Obesity in Humans,” Diabetes, Vol. 52, No. 6, 2003, pp. 1403-1408. doi:10.2337/diabetes.52.6.1403
- M. Markell, “New-Onset Diabetes Mellitus in Transplant Patients: Pathogenesis, Complications and Management,” American Journal of Kidney Diseases, Vol. 43, No. 6, 2004, pp. 953-965. doi:10.1053/j.ajkd.2004.03.020
- B. L. Kasiske, J. J. Snyder, D. Gilbertson and A. J. Matas, “Diabetes Mellitys after Kidney Transplantation in the United States,” American Journal of Transplantation, Vol. 3, No. 2, 2003, pp. 178-185. doi:10.1034/j.1600-6143.2003.00010.x
- J. Davidson, A. Wilkinson, J. Dantal, F. Dotta, H. Haller, D. Herna′ndez, et al., “New-Onset Diabetes after Transplantation: International Consensus Guidelines,” Transplantation, Vol. 75, 2003, p. SS3. doi:10.1097/01.TP.0000069952.49242.3E
- S. E. Kahn, “The Relative Contributions of Insulin Resistance and Beta Cell Dysfunction to the Pathophysiology of Type 2 Diabetes,” Diabetologia, Vol. 46, No. 1, 2003, pp. 3-19.
- A. V. Ekstrand, J. G. Eriksson, R. C. Gronhagen, P. J. Ahonen and L. C. Groop, “Insulin Resistance and Insulin Deficiency in the Pathogenesis of Post-Transplantation Diabetes in MA,” Transplantation, Vol. 53, No. 3, 1992, pp. 563-569. doi:10.1097/00007890-199203000-00014
- S. K. Enu, S. K. Myoung, S. K. Yu, H. K. Chul and C. L. Hyun, “A Polymorphism in the Zinc Transporter Gene SLC30A8 Confers Resistance against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients,” Diabetes, Vol. 57, No. 4, 2008, pp. 1043-1047.
- B. G. Marilia and A. CRoberta, “Post Transplant Diabetes Mellitus,” Diabetology & Metabolic syndrome, Vol. 1, No. , 2009, pp. 14.