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Published in: Acta Diabetologica 11/2018

01-11-2018 | Review Article

Advances in understanding the genetic basis of diabetic kidney disease

Authors: Man Li, Marcus G. Pezzolesi

Published in: Acta Diabetologica | Issue 11/2018

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Abstract

Diabetic kidney disease (DKD) is a devastating complication of Type 1 and Type 2 diabetes and leads to increased morbidity and mortality. Earlier work in families has provided strong evidence that heredity is a major determinant of DKD. Previous linkage analyses and candidate gene studies have identified potential DKD genes; however, such approaches have largely been unsuccessful. Genome-wide association studies (GWAS) have made significant contribution in identifying SNPs associated with common complex diseases. Thanks to advanced technology, new analytical approaches, and international research collaborations, many DKD GWASs have reported unique genes, highlighted novel biological pathways and suggested new disease mechanisms. This review summarizes the current state of GWAS technology; findings from GWASs of DKD and its related traits conducted over the past 15 years and discuss the future of this field.
Literature
1.
go back to reference Krolewski ASWJ (1997) Clinical features and epidemiology of diabetic nephropathy. In: Pickup JCWG (ed) Textbook of diabetes, vol 2, 2nd edn. Blackwell Scientific Publications, Oxford, pp 53.51–53.13 Krolewski ASWJ (1997) Clinical features and epidemiology of diabetic nephropathy. In: Pickup JCWG (ed) Textbook of diabetes, vol 2, 2nd edn. Blackwell Scientific Publications, Oxford, pp 53.51–53.13
2.
go back to reference Parving HHMM, Ritz E (2004) Diabetic nephropathy. In: BM B (ed) Brenner and Rector’s the kidney, 7th edn. Elsevier, Philadelphia, pp 1777–1818 Parving HHMM, Ritz E (2004) Diabetic nephropathy. In: BM B (ed) Brenner and Rector’s the kidney, 7th edn. Elsevier, Philadelphia, pp 1777–1818
3.
go back to reference Jones CA, Krolewski AS, Rogus J, Xue JL, Collins A, Warram JH (2005) Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause? Kidney Int 67(5):1684–1691CrossRefPubMed Jones CA, Krolewski AS, Rogus J, Xue JL, Collins A, Warram JH (2005) Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause? Kidney Int 67(5):1684–1691CrossRefPubMed
4.
go back to reference Fogarty DG, Rich SS, Hanna L, Warram JH, Krolewski AS (2000) Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure. Kidney Int 57(1):250–257CrossRefPubMed Fogarty DG, Rich SS, Hanna L, Warram JH, Krolewski AS (2000) Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure. Kidney Int 57(1):250–257CrossRefPubMed
5.
go back to reference Forsblom CM, Kanninen T, Lehtovirta M, Saloranta C, Groop LC (1999) Heritability of albumin excretion rate in families of patients with Type II diabetes. Diabetologia 42(11):1359–1366CrossRefPubMed Forsblom CM, Kanninen T, Lehtovirta M, Saloranta C, Groop LC (1999) Heritability of albumin excretion rate in families of patients with Type II diabetes. Diabetologia 42(11):1359–1366CrossRefPubMed
6.
go back to reference Hunter DJ, Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD (2002) Genetic contribution to renal function and electrolyte balance: a twin study. Clin Sci (Lond) 103(3):259–265CrossRef Hunter DJ, Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD (2002) Genetic contribution to renal function and electrolyte balance: a twin study. Clin Sci (Lond) 103(3):259–265CrossRef
7.
go back to reference Krolewski AS, Poznik GD, Placha G, Canani L, Dunn J, Walker W, Smiles A et al (2006) A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type II diabetes. Kidney Int 69(1):129–136CrossRefPubMed Krolewski AS, Poznik GD, Placha G, Canani L, Dunn J, Walker W, Smiles A et al (2006) A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type II diabetes. Kidney Int 69(1):129–136CrossRefPubMed
8.
go back to reference Langefeld CD, Beck SR, Bowden DW, Rich SS, Wagenknecht LE, Freedman BI (2004) Heritability of GFR and albuminuria in Caucasians with type 2 diabetes mellitus. Am J Kidney Dis 43(5):796–800CrossRefPubMed Langefeld CD, Beck SR, Bowden DW, Rich SS, Wagenknecht LE, Freedman BI (2004) Heritability of GFR and albuminuria in Caucasians with type 2 diabetes mellitus. Am J Kidney Dis 43(5):796–800CrossRefPubMed
9.
go back to reference Hipkiss AR, Preston JE, Himsworth DT, Worthington VC, Keown M, Michaelis J, Lawrence J et al (1998) Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann N Y Acad Sci 854:37–53CrossRefPubMed Hipkiss AR, Preston JE, Himsworth DT, Worthington VC, Keown M, Michaelis J, Lawrence J et al (1998) Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann N Y Acad Sci 854:37–53CrossRefPubMed
12.
32.
go back to reference Shimazaki A, Kawamura Y, Kanazawa A, Sekine A, Saito S, Tsunoda T, Koya D et al (2005) Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. Diabetes 54(4):1171–1178CrossRefPubMed Shimazaki A, Kawamura Y, Kanazawa A, Sekine A, Saito S, Tsunoda T, Koya D et al (2005) Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. Diabetes 54(4):1171–1178CrossRefPubMed
34.
go back to reference Tanaka N, Babazono T, Saito S, Sekine A, Tsunoda T, Haneda M, Tanaka Y et al (2003) Association of solute carrier family 12 (sodium/chloride) member 3 with diabetic nephropathy, identified by genome-wide analyses of single nucleotide polymorphisms. Diabetes 52(11):2848–2853CrossRefPubMed Tanaka N, Babazono T, Saito S, Sekine A, Tsunoda T, Haneda M, Tanaka Y et al (2003) Association of solute carrier family 12 (sodium/chloride) member 3 with diabetic nephropathy, identified by genome-wide analyses of single nucleotide polymorphisms. Diabetes 52(11):2848–2853CrossRefPubMed
35.
go back to reference Mueller PW, Rogus JJ, Cleary PA, Zhao Y, Smiles AM, Steffes MW, Bucksa J et al (2006) Genetics of Kidneys in Diabetes (GoKinD) study: a genetics collection available for identifying genetic susceptibility factors for diabetic nephropathy in type 1 diabetes. J Am Soc Nephrol 17(7):1782–1790. https://doi.org/10.1681/ASN.2005080822 CrossRefPubMed Mueller PW, Rogus JJ, Cleary PA, Zhao Y, Smiles AM, Steffes MW, Bucksa J et al (2006) Genetics of Kidneys in Diabetes (GoKinD) study: a genetics collection available for identifying genetic susceptibility factors for diabetic nephropathy in type 1 diabetes. J Am Soc Nephrol 17(7):1782–1790. https://​doi.​org/​10.​1681/​ASN.​2005080822 CrossRefPubMed
38.
go back to reference Maeda S, Araki S, Babazono T, Toyoda M, Umezono T, Kawai K, Imanishi M et al (2010) Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes. Diabetes 59(8):2075–2079. https://doi.org/10.2337/db10-0067 CrossRefPubMedPubMedCentral Maeda S, Araki S, Babazono T, Toyoda M, Umezono T, Kawai K, Imanishi M et al (2010) Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes. Diabetes 59(8):2075–2079. https://​doi.​org/​10.​2337/​db10-0067 CrossRefPubMedPubMedCentral
41.
go back to reference Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, Coresh J et al (2008) MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40(10):1185–1192CrossRefPubMed Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, Coresh J et al (2008) MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40(10):1185–1192CrossRefPubMed
42.
go back to reference Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, Oleksyk T et al (2008) MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 40(10):1175–1184CrossRefPubMedPubMedCentral Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, Oleksyk T et al (2008) MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 40(10):1175–1184CrossRefPubMedPubMedCentral
46.
go back to reference Shimazaki A, Tanaka Y, Shinosaki T, Ikeda M, Watada H, Hirose T, Kawamori R et al (2006) ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs. Kidney Int 70(10):1769–1776CrossRefPubMed Shimazaki A, Tanaka Y, Shinosaki T, Ikeda M, Watada H, Hirose T, Kawamori R et al (2006) ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs. Kidney Int 70(10):1769–1776CrossRefPubMed
48.
go back to reference Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K, Walk SF et al (2001) CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107(1):27–41CrossRefPubMed Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K, Walk SF et al (2001) CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107(1):27–41CrossRefPubMed
50.
go back to reference Leak TS, Perlegas PS, Smith SG, Keene KL, Hicks PJ, Langefeld CD, Mychaleckyj JC et al (2009) Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans. Ann Hum Genet 73(2):152–159CrossRefPubMedPubMedCentral Leak TS, Perlegas PS, Smith SG, Keene KL, Hicks PJ, Langefeld CD, Mychaleckyj JC et al (2009) Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans. Ann Hum Genet 73(2):152–159CrossRefPubMedPubMedCentral
51.
go back to reference Hanson RL, Millis MP, Young NJ, Kobes S, Nelson RG, Knowler WC, DiStefano JK (2010) ELMO1 variants and susceptibility to diabetic nephropathy in American Indians. Mol Genet Metab 101(4):383–390CrossRefPubMedPubMedCentral Hanson RL, Millis MP, Young NJ, Kobes S, Nelson RG, Knowler WC, DiStefano JK (2010) ELMO1 variants and susceptibility to diabetic nephropathy in American Indians. Mol Genet Metab 101(4):383–390CrossRefPubMedPubMedCentral
52.
go back to reference Pezzolesi MG, Katavetin P, Kure M, Poznik GD, Skupien J, Mychaleckyj JC, Rich SS et al (2009) Confirmation of genetic associations at ELMO1 in the GoKinD collection supports its role as a susceptibility gene in diabetic nephropathy. Diabetes 58(11):2698–2702CrossRefPubMedPubMedCentral Pezzolesi MG, Katavetin P, Kure M, Poznik GD, Skupien J, Mychaleckyj JC, Rich SS et al (2009) Confirmation of genetic associations at ELMO1 in the GoKinD collection supports its role as a susceptibility gene in diabetic nephropathy. Diabetes 58(11):2698–2702CrossRefPubMedPubMedCentral
71.
Metadata
Title
Advances in understanding the genetic basis of diabetic kidney disease
Authors
Man Li
Marcus G. Pezzolesi
Publication date
01-11-2018
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 11/2018
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-018-1193-0

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