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

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.

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K. Vattam, I. Khan, S. Movva, K. Mukkavali, S. Poornima, P. Rao, Q. Hasan and P. Upendram, "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," Open Journal of Nephrology, Vol. 3 No. 2, 2013, pp. 104-108. doi: 10.4236/ojneph.2013.32018.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] 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
[2] 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
[3] 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
[4] 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
[5] 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
[6] 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
[7] 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
[8] 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.
[9] 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
[10] 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.
[11] B. G. Marilia and A. CRoberta, “Post Transplant Diabetes Mellitus,” Diabetology & Metabolic syndrome, Vol. 1, No. , 2009, pp. 14.
[12] S. Chava, V. Mohan, N. Pasupuleti, M. MLatha, I. A. Khan, P. Upendram, A. Kumar, Y. R. Ahuja and Q. Hasan, “Evaluation of Aurora—A Gene Polymorphism and Esophageal Cancer Risk in a South Indian Population,” Genetic Testing and Molecular Biomarkers, Vol. 15, No. 3, 2011, pp. 185-189. doi:10.1089/gtmb.2010.0143
[13] J. S. Preetha, M. Sireesha, P. Nagarjuna, V. Bhavani, V. Sambasivan, R. A. You and Q. Hasan, “Regulation of IGF2 Transcript and Protein Expression by Altered Methylation in Breast,” Journal of Cancer Research and Clinical Oncology, Vol. 137, No. 2, 2011, pp. 339-345. doi:10.1007/s00432-010-0890-z
[14] M. A. Williams, C. Qiu, J. C. Dempsey and D. A. Luthy, “Familial Aggregation of Type 2 Diabetes and Chronic Hypertension in Women with Gestational Diabetes Mellitus,” The Journal of Reproductive Medicine, Vol. 48, No. 12, 2003, pp. 955-962.
[15] N. Vaessen, P. Heutink, J. A. Janssen, J. C. Witteman, L. Testers, A. Hofman, S. W. Lamberts, B. A. Oostra, H. A. Pols and C. M. Vanduijn, “A Polymorphism in the Gene for IGF1: Functional Properties and Risk for Type 2 Diabetes and Myocardial Infarction,” Diabetes, Vol. 50, No. 3, 2001, pp. 637-642. doi:10.2337/diabetes.50.3.637
[16] S. D. O’Dell, G. J. Miller, J. A. Cooper, P. C. Hindmarsh, P. J. Pringle, H. Ford, S. E. Humphries and I. N. Day, “Apa I Polymorphism in Insulin-Like Growth Factor II (IGF2) Gene and Weight in Middle-Aged Males,” International Journal of Obesity, Vol. 21, No. 9, 1997, pp. 822-825. doi:10.1038/sj.ijo.0800483
[17] T. R. Gaunt, J. A. Cooper, G. J. Miller, I. N. Day and S. D. O’Dell, “Positive Associations between Single Nucleotide Polymorphisms in the IGF2 Gene Region and Body Mass Index in Adult Males,” Human Molecular Genetics, Vol. 10, No. 14, 2001, pp. 1491-1501. doi:10.1093/hmg/10.14.1491
[18] O. Ukkola, G. Sun and C. Bouchard, “Insulin-Like Growth Factor 2 (IGF2) and IGF-Binding Protein 1 (IGFBP1) Gene Variants Are Associated with Overfeeding-Induced Metabolic Changes,” Diabetologia, Vol. 44, No. 12, 2001, pp. 2231-2236. doi:10.1007/s001250100034
[19] M. V. Gomes, M. R. Soares, N. A. Pasqualim, C. R. Marcondes, R. B. Lôbo and E. S. Ramos, “Association between Birth Weight, Body Mass Index and IGF2/ApaI Polymorphism,” Growth Hormone and IGF Research, Vol. 15, No. 5, 2005, pp. 360-362. doi:10.1016/j.ghir.2005.06.016
[20] S. Movva, S. Venkatasubramanian, K. K. Vattam, R. Sistla, Y. R. Ahuja and Q. Hasan, “Relevance of Insulin-Like Growth Factor 2 in the Etiopathophysiology of Diabetic Nephropathy: Possible Roles of Phosphatase and Tensin Homolog on Chromosome 10 and Secreted Protein Acidic and Rich in Cysteine as Regulators of Repair,” Journal of Diabetes, Vol. 1, No. 2, 2009, pp. 118124. doi:10.1111/j.1753-0407.2009.00025.x

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