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Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Editorial

Genomics in Diabetic Kidney Disease: A 2024 Update

Author(s): Stefanos Roumeliotis*, Maria Divani, Eleni Stamellou and Vassilios Liakopoulos

Volume 25, Issue 3, 2024

Published on: 02 April, 2024

Page: [153 - 157] Pages: 5

DOI: 10.2174/0113892029300247240325080421

Abstract

Diabetic Kidney Disease (DKD) remains the leading cause of Chronic and End Stage Kidney Disease (ESKD) worldwide, with an increasing epidemiological burden. However, still, the disease awareness remains low, early diagnosis is difficult, and therapeutic management is ineffective. These might be attributed to the fact that DKD is a highly heterogeneous disease, with disparities and variability in clinical presentation and progression patterns. Besides environmental risk factors, genetic studies have emerged as a novel and promising tool in the field of DKD. Three decades ago, family studies first reported that inherited genetic factors might confer significant risk to DKD development and progression. During the past decade, genome-wide association studies (GWASs) screening the whole genome in large and multi-ethnic population-based cohorts identified genetic risk variants associated with traits defining DKD in both type 1 and 2 diabetes. Herein, we aim to summarize the existing data regarding the progress in the field of genomics in DKD, present how the revolution of GWAS expanded our understanding of pathophysiologic disease mechanisms and finally, suggest potential future directions.

Keywords: Chronic kidney disease, diabetic kidney disease, end-stage kidney disease, genomics, GWAS, single nucleotide polymorphisms.

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[1]
Seaquist, E.R.; Goetz, F.C.; Rich, S.; Barbosa, J. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N. Engl. J. Med., 1989, 320(18), 1161-1165.
[http://dx.doi.org/10.1056/NEJM198905043201801] [PMID: 2710189]
[2]
Satko, S.G.; Sedor, J.R.; Iyengar, S.K.; Freedman, B.I. Familial clustering of chronic kidney disease. Semin. Dial., 2007, 20(3), 229-236.
[http://dx.doi.org/10.1111/j.1525-139X.2007.00282.x] [PMID: 17555489]
[3]
Williams, W.W.; Salem, R.M.; McKnight, A.J.; Sandholm, N.; Forsblom, C.; Taylor, A.; Guiducci, C.; McAteer, J.B.; McKay, G.J.; Isakova, T.; Brennan, E.P.; Sadlier, D.M.; Palmer, C.; Söderlund, J.; Fagerholm, E.; Harjutsalo, V.; Lithovius, R.; Gordin, D.; Hietala, K.; Kytö, J.; Parkkonen, M.; Rosengård-Bärlund, M.; Thorn, L.; Syreeni, A.; Tolonen, N.; Saraheimo, M.; Wadén, J.; Pitkäniemi, J.; Sarti, C.; Tuomilehto, J.; Tryggvason, K.; Österholm, A.M.; He, B.; Bain, S.; Martin, F.; Godson, C.; Hirschhorn, J.N.; Maxwell, A.P.; Groop, P.H.; Florez, J.C. Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy. Diabetes, 2012, 61(8), 2187-2194.
[http://dx.doi.org/10.2337/db11-0751] [PMID: 22721967]
[4]
Iyengar, S.K.; Sedor, J.R.; Freedman, B.I.; Kao, W.H.L.; Kretzler, M.; Keller, B.J.; Abboud, H.E.; Adler, S.G.; Best, L.G.; Bowden, D.W.; Burlock, A.; Chen, Y.D.I.; Cole, S.A.; Comeau, M.E.; Curtis, J.M.; Divers, J.; Drechsler, C.; Duggirala, R.; Elston, R.C.; Guo, X.; Huang, H.; Hoffmann, M.M.; Howard, B.V.; Ipp, E.; Kimmel, P.L.; Klag, M.J.; Knowler, W.C.; Kohn, O.F.; Leak, T.S.; Leehey, D.J.; Li, M.; Malhotra, A.; März, W.; Nair, V.; Nelson, R.G.; Nicholas, S.B.; O’Brien, S.J.; Pahl, M.V.; Parekh, R.S.; Pezzolesi, M.G.; Rasooly, R.S.; Rotimi, C.N.; Rotter, J.I.; Schelling, J.R.; Seldin, M.F.; Shah, V.O.; Smiles, A.M.; Smith, M.W.; Taylor, K.D.; Thameem, F.; Thornley-Brown, D.P.; Truitt, B.J.; Wanner, C.; Weil, E.J.; Winkler, C.A.; Zager, P.G.; Igo, R.P., Jr; Hanson, R.L.; Langefeld, C.D. Genome-wide association and trans-ethnic meta-analysis for advanced diabetic kidney disease: Family Investigation of Nephropathy and Diabetes (FIND). PLoS Genet., 2015, 11(8), e1005352.
[http://dx.doi.org/10.1371/journal.pgen.1005352] [PMID: 26305897]
[5]
Sandholm, N.; Salem, R.M.; McKnight, A.J.; Brennan, E.P.; Forsblom, C.; Isakova, T. New susceptibility loci associated with kidney disease in type 1 diabetes. PLoS Genet., 2012, 8(9), e1002921.
[http://dx.doi.org/10.1371/journal.pgen.1002921]
[6]
Salem, R.M.; Todd, J.N.; Sandholm, N.; Valo, E.; Haukka, J.K.; Harjutsalo, V. Genome-wide association study of diabetic kidney disease highlights biology involved in glomerular basement membrane collagen. J. Am. Soc. Nephrol., 2019, 30(10)
[http://dx.doi.org/10.1681/ASN.2019030218]
[7]
Xue, D.; Narisu, N.; Taylor, D.L.; Zhang, M.; Grenko, C.; Taylor, H.J.; Yan, T.; Tang, X.; Sinha, N.; Zhu, J.; Vandana, J.J.; Nok Chong, A.C.; Lee, A.; Mansell, E.C.; Swift, A.J.; Erdos, M.R.; Zhong, A.; Bonnycastle, L.L.; Zhou, T.; Chen, S.; Collins, F.S. Functional interrogation of twenty type 2 diabetes-associated genes using isogenic human embryonic stem cell-derived β-like cells. Cell Metab., 2023, 35(11), 1897-1914.e11.
[http://dx.doi.org/10.1016/j.cmet.2023.09.013] [PMID: 37858332]
[8]
Wei, L.; Xiao, Y.; Li, L.; Xiong, X.; Han, Y.; Zhu, X.; Sun, L. The susceptibility genes in diabetic nephropathy. Kidney Dis., 2018, 4(4), 226-237.
[http://dx.doi.org/10.1159/000492633] [PMID: 30574499]
[9]
Jin, H.; Kim, Y.A.; Lee, Y.; Kwon, S.; Do, A.R.; Seo, S.; Won, S.; Seo, J.H. Identification of genetic variants associated with diabetic kidney disease in multiple Korean cohorts via a genome-wide association study mega-analysis. BMC Med., 2023, 21(1), 16.
[http://dx.doi.org/10.1186/s12916-022-02723-4] [PMID: 36627639]
[10]
Tziastoudi, M.; Stefanidis, I.; Zintzaras, E. The genetic map of diabetic nephropathy: Evidence from a systematic review and meta-analysis of genetic association studies. Clin. Kidney J., 2020, 13(5), 768-781.
[http://dx.doi.org/10.1093/ckj/sfaa077] [PMID: 33123356]
[11]
Roumeliotis, A.; Roumeliotis, S.; Tsetsos, F.; Georgitsi, M.; Georgianos, P.I.; Stamou, A.; Vasilakou, A.; Kotsa, K.; Tsekmekidou, X.; Paschou, P.; Panagoutsos, S.; Liakopoulos, V. Oxidative stress genes in Diabetes Mellitus Type 2: Association with diabetic kidney disease. Oxid. Med. Cell. Longev., 2021, 2021, 1-10.
[http://dx.doi.org/10.1155/2021/2531062] [PMID: 34545296]
[12]
Roumeliotis, S.; Roumeliotis, A.; Stamou, A.; Panagoutsos, S.; Manolopoulos, V.G.; Tsetsos, F.; Georgitsi, M.; Liakopoulos, V. Association of rs11780592 Polymorphism in the Human Soluble Epoxide Hydrolase Gene (EPHX2) with Oxidized LDL and Mortality in Patients with Diabetic Chronic Kidney Disease. Oxid. Med. Cell. Longev., 2021, 2021, 1-8.
[http://dx.doi.org/10.1155/2021/8817502] [PMID: 34040693]
[13]
Tsekmekidou, X.; Tsetsos, F.; Koufakis, T.; Karras, S.N.; Georgitsi, M.; Papanas, N.; Papazoglou, D.; Roumeliotis, A.; Panagoutsos, S.; Thodis, E.; Theodoridis, M.; Pasadakis, P.; Maltezos, E.; Paschou, P.; Kotsa, K. Association between CUBN gene variants, type 2 diabetes and vitamin D concentrations in an elderly Greek population. J. Steroid Biochem. Mol. Biol., 2020, 198, 105549.
[http://dx.doi.org/10.1016/j.jsbmb.2019.105549] [PMID: 31770575]
[14]
Lindhardt, M.; Persson, F.; Oxlund, C.; Jacobsen, I.A.; Zürbig, P.; Mischak, H.; Rossing, P.; Heerspink, H.J.L. Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension. Nephrol. Dial. Transplant., 2018, 33(2), 296-303.
[PMID: 28064163]
[15]
Pena, M.J.; Heinzel, A.; Rossing, P.; Parving, H.H.; Dallmann, G.; Rossing, K.; Andersen, S.; Mayer, B.; Heerspink, H.J.L. Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus. J. Transl. Med., 2016, 14(1), 203.
[http://dx.doi.org/10.1186/s12967-016-0960-3] [PMID: 27378474]
[16]
Andersen, S.; Mischak, H.; Zürbig, P.; Parving, H.H.; Rossing, P. Urinary proteome analysis enables assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria. BMC Nephrol., 2010, 11(1), 29.
[http://dx.doi.org/10.1186/1471-2369-11-29] [PMID: 21040538]
[17]
Winkler, T.W.; Rasheed, H.; Teumer, A.; Gorski, M.; Rowan, B.X.; Stanzick, K.J.; Thomas, L.F.; Tin, A.; Hoppmann, A.; Chu, A.Y.; Tayo, B.; Thio, C.H.L.; Cusi, D.; Chai, J.F.; Sieber, K.B.; Horn, K.; Li, M.; Scholz, M.; Cocca, M.; Wuttke, M.; van der Most, P.J.; Yang, Q.; Ghasemi, S.; Nutile, T.; Li, Y.; Pontali, G.; Günther, F.; Dehghan, A.; Correa, A.; Parsa, A.; Feresin, A.; de Vries, A.P.J.; Zonderman, A.B.; Smith, A.V.; Oldehinkel, A.J.; De Grandi, A.; Rosenkranz, A.R.; Franke, A.; Teren, A.; Metspalu, A.; Hicks, A.A.; Morris, A.P.; Tönjes, A.; Morgan, A.; Podgornaia, A.I.; Peters, A.; Körner, A.; Mahajan, A.; Campbell, A.; Freedman, B.I.; Spedicati, B.; Ponte, B.; Schöttker, B.; Brumpton, B.; Banas, B.; Krämer, B.K.; Jung, B.; Åsvold, B.O.; Smith, B.H.; Ning, B.; Penninx, B.W.J.H.; Vanderwerff, B.R.; Psaty, B.M.; Kammerer, C.M.; Langefeld, C.D.; Hayward, C.; Spracklen, C.N.; Robinson-Cohen, C.; Hartman, C.A.; Lindgren, C.M.; Wang, C.; Sabanayagam, C.; Heng, C.K.; Lanzani, C.; Khor, C.C.; Cheng, C.Y.; Fuchsberger, C.; Gieger, C.; Shaffer, C.M.; Schulz, C.A.; Willer, C.J.; Chasman, D.I.; Gudbjartsson, D.F.; Ruggiero, D.; Toniolo, D.; Czamara, D.; Porteous, D.J.; Waterworth, D.M.; Mascalzoni, D.; Mook-Kanamori, D.O.; Reilly, D.F.; Daw, E.W.; Hofer, E.; Boerwinkle, E.; Salvi, E.; Bottinger, E.P.; Tai, E.S.; Catamo, E.; Rizzi, F.; Guo, F.; Rivadeneira, F.; Guilianini, F.; Sveinbjornsson, G.; Ehret, G.; Waeber, G.; Biino, G.; Girotto, G.; Pistis, G.; Nadkarni, G.N.; Delgado, G.E.; Montgomery, G.W.; Snieder, H.; Campbell, H.; White, H.D.; Gao, H.; Stringham, H.M.; Schmidt, H.; Li, H.; Brenner, H.; Holm, H.; Kirsten, H.; Kramer, H.; Rudan, I.; Nolte, I.M.; Tzoulaki, I.; Olafsson, I.; Martins, J.; Cook, J.P.; Wilson, J.F.; Halbritter, J.; Felix, J.F.; Divers, J.; Kooner, J.S.; Lee, J.J.M.; O’Connell, J.; Rotter, J.I.; Liu, J.; Xu, J.; Thiery, J.; Ärnlöv, J.; Kuusisto, J.; Jakobsdottir, J.; Tremblay, J.; Chambers, J.C.; Whitfield, J.B.; Gaziano, J.M.; Marten, J.; Coresh, J.; Jonas, J.B.; Mychaleckyj, J.C.; Christensen, K.; Eckardt, K.U.; Mohlke, K.L.; Endlich, K.; Dittrich, K.; Ryan, K.A.; Rice, K.M.; Taylor, K.D.; Ho, K.; Nikus, K.; Matsuda, K.; Strauch, K.; Miliku, K.; Hveem, K.; Lind, L.; Wallentin, L.; Yerges-Armstrong, L.M.; Raffield, L.M.; Phillips, L.S.; Launer, L.J.; Lyytikäinen, L.P.; Lange, L.A.; Citterio, L.; Klaric, L.; Ikram, M.A.; Ising, M.; Kleber, M.E.; Francescatto, M.; Concas, M.P.; Ciullo, M.; Piratsu, M.; Orho-Melander, M.; Laakso, M.; Loeffler, M.; Perola, M.; de Borst, M.H.; Gögele, M.; Bianca, M.L.; Lukas, M.A.; Feitosa, M.F.; Biggs, M.L.; Wojczynski, M.K.; Kavousi, M.; Kanai, M.; Akiyama, M.; Yasuda, M.; Nauck, M.; Waldenberger, M.; Chee, M.L.; Chee, M.L.; Boehnke, M.; Preuss, M.H.; Stumvoll, M.; Province, M.A.; Evans, M.K.; O’Donoghue, M.L.; Kubo, M.; Kähönen, M.; Kastarinen, M.; Nalls, M.A.; Kuokkanen, M.; Ghanbari, M.; Bochud, M.; Josyula, N.S.; Martin, N.G.; Tan, N.Y.Q.; Palmer, N.D.; Pirastu, N.; Schupf, N.; Verweij, N.; Hutri-Kähönen, N.; Mononen, N.; Bansal, N.; Devuyst, O.; Melander, O.; Raitakari, O.T.; Polasek, O.; Manunta, P.; Gasparini, P.; Mishra, P.P.; Sulem, P.; Magnusson, P.K.E.; Elliott, P.; Ridker, P.M.; Hamet, P.; Svensson, P.O.; Joshi, P.K.; Kovacs, P.; Pramstaller, P.P.; Rossing, P.; Vollenweider, P.; van der Harst, P.; Dorajoo, R.; Sim, R.Z.H.; Burkhardt, R.; Tao, R.; Noordam, R.; Mägi, R.; Schmidt, R.; de Mutsert, R.; Rueedi, R.; van Dam, R.M.; Carroll, R.J.; Gansevoort, R.T.; Loos, R.J.F.; Felicita, S.C.; Sedaghat, S.; Padmanabhan, S.; Freitag-Wolf, S.; Pendergrass, S.A.; Graham, S.E.; Gordon, S.D.; Hwang, S.J.; Kerr, S.M.; Vaccargiu, S.; Patil, S.B.; Hallan, S.; Bakker, S.J.L.; Lim, S.C.; Lucae, S.; Vogelezang, S.; Bergmann, S.; Corre, T.; Ahluwalia, T.S.; Lehtimäki, T.; Boutin, T.S.; Meitinger, T.; Wong, T.Y.; Bergler, T.; Rabelink, T.J.; Esko, T.; Haller, T.; Thorsteinsdottir, U.; Völker, U.; Foo, V.H.X.; Salomaa, V.; Vitart, V.; Giedraitis, V.; Gudnason, V.; Jaddoe, V.W.V.; Huang, W.; Zhang, W.; Wei, W.B.; Kiess, W.; März, W.; Koenig, W.; Lieb, W.; Gao, X.; Sim, X.; Wang, Y.X.; Friedlander, Y.; Tham, Y.C.; Kamatani, Y.; Okada, Y.; Milaneschi, Y.; Yu, Z.; Thio, C.H.L.; van der Most, P.J.; de Borst, M.H.; Ho, K.; Josyula, N.S.; Pendergrass, S.A.; Rowan, B.X.; Robinson-Cohen, C.; Gaziano, J.M.; Phillips, L.S.; Tao, R.; Hung, A.M.; Stark, K.J.; Stefansson, K.; Böger, C.A.; Hung, A.M.; Kronenberg, F.; Köttgen, A.; Pattaro, C.; Heid, I.M. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals. Commun. Biol., 2022, 5(1), 580.
[http://dx.doi.org/10.1038/s42003-022-03448-z] [PMID: 35697829]
[18]
Friedman, D.J.; Pollak, M.R. APOL1 nephropathy: From genetics to clinical applications. Clin. J. Am. Soc. Nephrol., 2021, 16(2), 294-303.
[http://dx.doi.org/10.2215/CJN.15161219] [PMID: 32616495]
[19]
Parsa, A.; Kao, W.H.L.; Xie, D.; Astor, B.C.; Li, M.; Hsu, C.; Feldman, H.I.; Parekh, R.S.; Kusek, J.W.; Greene, T.H.; Fink, J.C.; Anderson, A.H.; Choi, M.J.; Wright, J.T., Jr; Lash, J.P.; Freedman, B.I.; Ojo, A.; Winkler, C.A.; Raj, D.S.; Kopp, J.B.; He, J.; Jensvold, N.G.; Tao, K.; Lipkowitz, M.S.; Appel, L.J. APOL1 risk variants, race, and progression of chronic kidney disease. N. Engl. J. Med., 2013, 369(23), 2183-2196.
[http://dx.doi.org/10.1056/NEJMoa1310345] [PMID: 24206458]
[20]
Bruggeman, L.A.; Sedor, J.R.; O’Toole, J.F. Apolipoprotein L1 and mechanisms of kidney disease susceptibility. Curr. Opin. Nephrol. Hypertens., 2021, 30(3), 317-323.
[http://dx.doi.org/10.1097/MNH.0000000000000704] [PMID: 33767059]
[21]
Freedman, B.I.; Pastan, S.O.; Israni, A.K.; Schladt, D.; Julian, B.A.; Gautreaux, M.D.; Hauptfeld, V.; Bray, R.A.; Gebel, H.M.; Kirk, A.D.; Gaston, R.S.; Rogers, J.; Farney, A.C.; Orlando, G.; Stratta, R.J.; Mohan, S.; Ma, L.; Langefeld, C.D.; Bowden, D.W.; Hicks, P.J.; Palmer, N.D.; Palanisamy, A.; Reeves-Daniel, A.M.; Brown, W.M.; Divers, J. APOL1 genotype and kidney transplantation outcomes from deceased African American donors. Transplantation, 2016, 100(1), 194-202.
[http://dx.doi.org/10.1097/TP.0000000000000969] [PMID: 26566060]
[22]
Freedman, B.I.; Moxey-Mims, M.M.; Alexander, A.A.; Astor, B.C.; Birdwell, K.A.; Bowden, D.W.; Bowen, G.; Bromberg, J.; Craven, T.E.; Dadhania, D.M.; Divers, J.; Doshi, M.D.; Eidbo, E.; Fornoni, A.; Gautreaux, M.D.; Gbadegesin, R.A.; Gee, P.O.; Guerra, G.; Hsu, C.; Iltis, A.S.; Jefferson, N.; Julian, B.A.; Klassen, D.K.; Koty, P.P.; Langefeld, C.D.; Lentine, K.L.; Ma, L.; Mannon, R.B.; Menon, M.C.; Mohan, S.; Moore, J.B.; Murphy, B.; Newell, K.A.; Odim, J.; Ortigosa-Goggins, M.; Palmer, N.D.; Park, M.; Parsa, A.; Pastan, S.O.; Poggio, E.D.; Rajapakse, N.; Reeves-Daniel, A.M.; Rosas, S.E.; Russell, L.P.; Sawinski, D.; Smith, S.C.; Spainhour, M.; Stratta, R.J.; Weir, M.R.; Reboussin, D.M.; Kimmel, P.L.; Brennan, D.C. APOL1 long-term kidney transplantation outcomes network (APOLLO): Design and rationale. Kidney Int. Rep., 2020, 5(3), 278-288.
[http://dx.doi.org/10.1016/j.ekir.2019.11.022] [PMID: 32154449]
[23]
Ali, A.S.; Pham, C.; Morahan, G.; Ekinci, E.I. Genetic risk scores identify people at high risk of developing diabetic kidney disease: A systematic review. J. Clin. Endocrinol. Metab., 2023, 109(5), 1189-1197.
[http://dx.doi.org/10.1210/clinem/dgad704] [PMID: 38039081]

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