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Genetic factors in the development of chronic kidney disease in patients with diabetes mellitus

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Abstract

Patients with diabetes mellitus (DM) represent a risk group for developing chronic kidney disease (CKD), the terminal stages of which require renal replacement therapy. The study of genetic predisposition to CKD is of special significance from the perspective of the prediction and identification of risk groups at the preclinical stage. The present study is a review of the world literature on the genetics of CKD in diabetes and also includes data of our own studies.

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References

  1. Dedov, I.I., Shestakova, M.V., and Vikulova, O.K., National register of diabetes mellitus in Russian Federation: status in 2014 and the perspectives, Sakh. Diabet, 2015, vol. 18, no. 3, pp. 5–23.

    Google Scholar 

  2. Seaquist, E.R., Goetz, F.C., Rish, S., and Barbosa, J., Familial clustering of diabetic kidney disease: evidence for genetic susceptibility to diabetic nephropathy, N. Engl. J. Med., 1989, vol. 320, pp. 1161–1165. doi 10.1056/NEJM198905043201801

    Article  CAS  PubMed  Google Scholar 

  3. Shestakova, M.V., The modem concept of “chronic kidney disease”: diagnostic methods, clinical significance, Sakh. Diabet, 2008, vol. 11, no. 2, pp. 4–7. doi 10.14341/2072-0351-5750

    Google Scholar 

  4. Shestakova, M.V., Vikulova, O.K., Gorashko, N.M., et al., The relationship between genetic and haemodynamic factors in diabetic nephropathy (DN): case–control study in type 1 diabetes mellitus (T1DM), Diabetes Res. Clin. Pract., 2006, vol. 74, pp. S41–S50.

    Article  CAS  Google Scholar 

  5. McKnight, A.J., Duffy, S., and Maxwell, A.P., Genetics of diabetic nephropathy: a long road of discovery, Curr. Diabetes Rep., 2015, vol. 15, vol. 7, p. 41. doi 10.1007/s11892-015-0610-9

    Article  Google Scholar 

  6. Shestakova, M.V., Renin–angiotensin–aldosterone system: evolution of views from renin discovery to nowadays. Perspectives of therapeutic block, Ter. Arkh., 2011, vol. 83, no. 4, pp. 71–77.

    CAS  PubMed  Google Scholar 

  7. Rahimi, Z., ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy, J. Nephropathol., 2012, vol. 1, no. 3, pp. 143–151. doi 10.5812/nephropathol. 8109

    Article  PubMed  PubMed Central  Google Scholar 

  8. O’Donnell, C.J., Lindpaintner, K., Larson, M.G., et al., Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study, Circulation, 1998, vol. 97, pp. 1766–1772. doi 10.1161/01.CIR.97.18.1766

    Article  PubMed  Google Scholar 

  9. Gürlek, A., Güleç, S., Karabulut, H., et al., Relation between the insertion/deletion polymorphism of the angiotensin I converting enzyme gene and restenosis after coronary stenting, J. Cardiovasc. Risk, 2000, vol. 7, no. 6, pp. 403–407.

    Article  PubMed  Google Scholar 

  10. Yu, Z.Y., Chen, L.S., Zhang, L.C., and Zhou, T.B., Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy, Nephrology (Carlton), 2012, vol. 17, no. 5, pp. 480–487. doi 10.1111/j.1440-1797.2012.01592.x

    Article  Google Scholar 

  11. Lin, C., Yang, H.Y., Wu, C.C., et al., Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension—a meta-regression analysis of 98 observational studies, PLoS One, 2014, vol. 9, no. 1. e87604. doi 10.1371/journal.pone.0087604

    Article  PubMed  PubMed Central  Google Scholar 

  12. Shaikh, R., Shahid, S., Mansoor, Q., et al., Genetic variants of ACE (Insertion/Deletion) and AGT (M268T) genes in patients with diabetes and nephropathy, J. Renin–Angiotensin–Aldosterone Syst., 2014, vol. 15, no. 2, pp. 124–130. doi 10.1177/ 1470320313512390

    CAS  PubMed  Google Scholar 

  13. Pettersson-Fernholm, K., Fröjdö, S., Fagerudd, J., et al., The AT2 gene may have a gender-specific effect on kidney function and pulse pressure in type I diabetic patients, Kidney Int., 2006, vol. 69, pp. 1880–1884. doi 10.1038/sj.ki.5000348

    Article  CAS  PubMed  Google Scholar 

  14. Miyahara, K., Kawamoto, T., and Sase, K., Cloning and structural characterization of the human endothelial nitric-oxide-synthase gene, Eur. J. Biochem., 1994, vol. 223, pp. 719–726.

    Article  CAS  PubMed  Google Scholar 

  15. Wang, X.L., Sim, A.S., Wang, M.X., et al., Genotype dependent and cigarette specific effects on endothelial nitric oxide synthase gene expression and enzyme activity, FEBS Lett., 2000, vol. 471, pp. 45–50. doi 10.1016/S0014-5793(00)01356-9

    Article  CAS  PubMed  Google Scholar 

  16. Zintzaras, E., Papathanasiou, A.A., and Stefanidis, I., Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: a HuGE review and metaanalysis, Genet. Med., 2009, vol. 11, no. 10, pp. 695–706. doi 10.1097/GIM.0b013e3181b2046b

    Article  CAS  PubMed  Google Scholar 

  17. Ma, Z., Chen, R., Ren, H., et al., Endothelial nitric oxide synthase (eNOS) 4b/a polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus: a meta-analysis, Meta Gene, 2014, vol. 2, pp. 50–62. 10.1016/j.mgene.2013.10.015

    Article  PubMed  Google Scholar 

  18. Zheleznyakova, A.V., Lebedeva, N.O., Vikulova, O.K., et al., Risk of chronic kidney disease in type 2 diabetes determined by polymorphisms in NOS3, APOB, KCNJ11, TCF7L2 genes as compound effect of risk genotypes combination, Sakh. Diabet, 2014, vol. 17, no. 3, pp. 23–30. doi 10.14341/DM2014323-30

    Google Scholar 

  19. Demaine, A.G., Polymorphisms of the aldose reductase gene and susceptibility to diabetic microvascular complications, Curr. Med. Chem., 2003, vol. 10, pp. 1389–1398. doi 10.2174/0929867033457359

    Article  CAS  PubMed  Google Scholar 

  20. Keane, W.F., Tomassini, J.E., and Neff, D.R., Lipid abnormalities in patients with chronic kidney disease: implications for the pathophysiology of atherosclerosis, J. Atheroscler. Thromb., 2013, vol. 20, no. 2, pp. 123–133. doi 10.5551/jat.12849

    Article  CAS  PubMed  Google Scholar 

  21. Boekholdt, S.M., Peters, R.J.G., Fountoulaki, K., et al., Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis, Hum. Genet., 2003, vol. 113, pp. 417–425.

    Article  CAS  PubMed  Google Scholar 

  22. Bernard, S., Charrière, S., Charcosset, M., et al., Relation between apolipoprotein B gene polymorphism and cardiovascular risk in a type 2 diabetic cohort, Atherosclerosis, 2004, vol. 175, no. 1, p. 177.

    Article  CAS  PubMed  Google Scholar 

  23. Yakunina, N.Yu., Shestakova, M.V., Voron’ko, O.E., et al., Polymorphic gene markers of lipid metabolism are associated with diabetic nephropathy in patients with type 1 diabetes mellitus, Russ. J. Genet., 2005, vol. 41, no. 7, pp. 760–765.

    Article  CAS  Google Scholar 

  24. Michaelson, D.M., APOE ε4: the most prevalent yet understudied risk factor for Alzheimer’s disease, Alzheimers Dement., 2014, vol. 10, no. 6, pp. 861–868. doi 10.1016/j.jalz.2014.06.015

    Article  PubMed  Google Scholar 

  25. Lahoz, C., Schaefer, E.J., Cupples, L.A., et al., Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study, Atherosclerosis, 2001, vol. 154, no. 3, pp. 529–537.

    Article  CAS  PubMed  Google Scholar 

  26. Araki, S.I., Koya, D., Makiishi, T., et al., APOE polymorphism and the progression of diabetic nephropathy in Japanese subjects with type 2 diabetes results of a prospective observational follow-up study, Diabetes Care, 2003, vol. 26, pp. 2416–2420. doi 10.2337/diacare.26.8.2416

    Article  CAS  PubMed  Google Scholar 

  27. Mooyaart, A.L., Valk, E.J., van Es, L.A., et al., Genetic associations in diabetic nephropathy: a meta-analysis, Diabetologia, 2011, vol. 54, pp. 544–553. doi 10.1007/s00125-010-1996-1

    Article  CAS  PubMed  Google Scholar 

  28. McKnight, A.J., McKay, J.G., and Maxwell, A.P., Genetic and epigenetic risk factors for diabetic kidney disease, Adv. Chronic Kidney Dis., 2014, vol. 21, no. 3, pp. 287–296. doi 10.1053/j.ackd.2014.03.010

    Article  PubMed  Google Scholar 

  29. Franceschini, N., Shara, N., Wang, H., et al., The association of genetic variants of type 2 diabetes with kidney function, Kidney Int., 2012, vol. 82, no. 2, pp. 220–225. doi 10.1038/ki.2012.107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Seino, S. and Miki, T., Physiological and pathophysiological roles of ATP-sensitive K+ channels, Prog. Biophys. Mol. Biol., 2003, vol. 8, pp. 133–176. doi 10.1016/S0079-6107(02)00053-6

    Article  Google Scholar 

  31. Flanagan, S., Clauin, S., Bellanne-Chantelot, C., et al., Update of mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism, Hum. Mutat., 2009, vol. 30, vol. 2, pp. 170–180. doi 10.1002/humu. 20838

    Article  CAS  PubMed  Google Scholar 

  32. Sokolova, E.A., Bondar, I.A., Shabelnikova, O.Y., et al., Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) association in Russian diabetes mellitus 2 type cohort and meta-analysis, PLoS One, 2015, vol. 10, no. 5. e0124662. doi 10.1371/journal.pone. 0124662

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bondar’, I.A. and Klimontov, V.V., Early markers of diabetic nephropathy, Klin. Nefrol., 2010, vol. 2, pp. 60–65.

    Google Scholar 

  34. Nazir, N., Siddiqui, K., Al-Qasim, S., and Al-Naqeb, D., Meta-analysis of diabetic nephropathy associated genetic variants in inflammation and angiogenesis involved in different biochemical pathways, BMC Med. Genet., 2014, vol. 15, p. 103. doi 10.1186/s12881-014-0103-8

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lebedeva, N.O. and Vikulova, O.K., Pre-clinical markers for diagnosis of diabetic nephropathy in patients with type 1 diabetes mellitus, Sakh. Diabet, 2012, vol. 15, no. 2, pp. 38–45. doi 10.14341/2072- 0351-5517

    Google Scholar 

  36. Jin, T. and Liu, L., Minireview: the Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus, Mol. Endocrinol., 2008, vol. 22, no. 11, pp. 2383–2392. doi 10.1210/me.2008-0135

    Article  CAS  PubMed  Google Scholar 

  37. Cauchi, S. and Froguel, P., TCF7L2 genetic defect and type 2 diabetes, Curr. Diabetes Rep., 2008, vol. 8, pp. 149–155.

    Article  CAS  Google Scholar 

  38. Groves, C.J., Zeggini, E., Minton, J., et al., Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk, Diabetes, 2006, vol. 55, pp. 2640–2644. doi 10.2337/db06- 0355

    Article  CAS  PubMed  Google Scholar 

  39. Nikitin, A.G., Potapov, V.A., Brovkin, A.N., et al., Association of the polymorphisms of the TCF7L2 genes with type 2 diabetes, Klin. Prakt., 2014, vol. 1, no. 17, pp. 4–11.

    Google Scholar 

  40. Florez, J.C., Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes?, Diabetologia, 2008, vol. 51, vol. 7, pp. 1100–1110. doi 10.1007/s00125-008- 1025-9

    Article  CAS  PubMed  Google Scholar 

  41. Freathy, R.M., Timpson, N.J., Lawlor, D.A., et al., Common variation in the FTO gene alters diabetesrelated metabolic traits to the extent expected, given its effect on BMI, Diabetes, 2008, vol. 57, pp. 1419–1426. 10.2337/db07-1466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Smyth, L.J., Duffy, S., Maxwell, A.P., and McKnight, A.J., Genetic and epigenetic factors influencing chronic kidney disease, Am. J. Physiol. Renal. Physiol., 2014, vol. 307, pp. F757–F776. doi 10.1152/ajprenal. 00306.2014

    Article  CAS  PubMed  Google Scholar 

  43. Tregouet, D.A., Groop, P.H., McGinn, S., et al., G/T substitution in intron 1 of the UNC13B gene is associated with increased risk of nephropathy in patients with type 1 diabetes, Diabetes, 2008, vol. 57, no. 10, pp. 2843–2850. doi 10.2337/db08-0073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bonomo, J.A., Ng, M.C., Palmer, N.D., et al., Coding variants in nephrin (NPHS1) and susceptibility to nephropathy in African Americans, Clin. J. Am. Soc. Nephrol., 2014, vol. 9, no. 8, pp. 1434–1440. doi 10.2215/CJN.00290114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Pezzolesi, M.G., Poznik, G.D., Mychaleckyj, J.C., et al., Genome-wide association scan for diabetic nephropathy susceptibility genes in type 1 diabetes, Diabetes, 2009, vol. 58, pp. 1403–1410. doi 10.2337/db08-1514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. McDonough, C.W., Palmer, N.D., Hicks, P.J., et al., A genome-wide association study for diabetic nephropathy genes in African Americans, Kidney Int., 2011, vol. 79, no. 5, pp. 563–572. doi 10.1038/ki.2010.467

    Article  PubMed  Google Scholar 

  47. Palmer, N.D., Ng, M.C., Hicks, P.J., et al., Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease, PLoS One, 2014, vol. 9, no. 2. e88273. doi 10.1371/journal.pone.0088273

    Article  PubMed  PubMed Central  Google Scholar 

  48. Martini, S., Nair, V., Patel, S.R., et al., From single nucleotide polymorphism to transcriptional mechanism: a model for FRMD3 in diabetic nephropathy, Diabetes, 2013, vol. 62, no. 7, pp. 2605–2612. doi 10.2337/db12-1416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Freedman, B.I., Bostrom, M., Daeihagh, P., et al., Genetic factors in diabetic nephropathy, Clin. J. Am. Soc. Nephrol., 2007, vol. 2, pp. 1306–1316. doi 10.2215/CJN.02560607

    Article  CAS  PubMed  Google Scholar 

  50. Wu, L.S.-H., Hsieh, C.-H., Pei, D., Hung, Y.-J., Association and interaction analyses of genetic variants in ADIPOQ, ENPP1 GHSR, PPARγ and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes, Nephrol. Dial. Transplant., 2009, vol. 24, pp. 3360–3366. doi 10.1093/ndt/gfp271

    Article  CAS  PubMed  Google Scholar 

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Correspondence to A. V. Zheleznyakova.

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Original Russian Text © O.K. Vikulova, A.V. Zheleznyakova, N.O. Lebedeva, A.G. Nikitin, V.V. Nosikov, M.V. Shestakova, 2017, published in Genetika, 2017, Vol. 53, No. 4, pp. 411–425.

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Vikulova, O.K., Zheleznyakova, A.V., Lebedeva, N.O. et al. Genetic factors in the development of chronic kidney disease in patients with diabetes mellitus. Russ J Genet 53, 420–432 (2017). https://doi.org/10.1134/S1022795417030140

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