Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
Vyšlo v časopise:
Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD. PLoS Genet 7(9): e32767. doi:10.1371/journal.pgen.1002292
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002292
Souhrn
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
Zdroje
1. LeveyASAtkinsRCoreshJCohenEPCollinsAJ 2007 Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 72 247 59
2. MatsushitaKvan der VeldeMAstorBCWoodwardMLeveyAS 2010 Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375 2073 81
3. BaumeisterSEBögerCAKrämerBKDoringAEhebergD 2010 Effect of chronic kidney disease and comorbid conditions on health care costs: A 10-year observational study in a general population. Am J Nephrol 31 222 9
4. Meguid El NahasABelloAK 2005 Chronic kidney disease: the global challenge. Lancet 365 331 40
5. AdlerAIStevensRJManleySEBilousRWCullCA 2003 Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 63 225 32
6. HsuCYMcCullochCEDarbinianJGoASIribarrenC 2005 Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease. Arch Intern Med 165 923 8
7. KastarinenMJuutilainenAKastarinenHSalomaaVKarhapaaP Risk factors for end-stage renal disease in a community-based population: 26-year follow-up of 25,821 men and women in eastern Finland. J Intern Med 267 612 20
8. RitzEStefanskiA 1996 Diabetic nephropathy in type II diabetes. Am J Kidney Dis 27 167 94
9. CoreshJSelvinEStevensLAManziJKusekJW 2007 Prevalence of chronic kidney disease in the United States. JAMA 298 2038 47
10. FoxCSLarsonMGLeipEPCulletonBWilsonPW 2004 Predictors of new-onset kidney disease in a community-based population. JAMA 291 844 50
11. FoxCSMuntnerP 2008 Trends in diabetes, high cholesterol, and hypertension in chronic kidney disease among U.S. adults: 1988-1994 to 1999-2004. Diabetes Care 31 1337 42
12. SatkoSGSedorJRIyengarSKFreedmanBI 2007 Familial clustering of chronic kidney disease. Semin Dial 20 229 36
13. GenoveseGFriedmanDJRossMDLecordierLUzureauP 2010 Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329 841 5
14. KaoWHKlagMJMeoniLAReichDBerthier-SchaadY 2008 MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40 1185 92
15. KoppJBSmithMWNelsonGWJohnsonRCFreedmanBI 2008 MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 40 1175 84
16. KöttgenAGlazerNLDehghanAHwangSJKatzR 2009 Multiple loci associated with indices of renal function and chronic kidney disease. Nat Genet 41 712 7
17. KöttgenAPattaroCBögerCAFuchsbergerCOldenM 2010 New loci associated with kidney function and chronic kidney disease. Nat Genet 42 376 84
18. ChambersJCZhangWLordGMvan der HarstPLawlorDA 2010 Genetic loci influencing kidney function and chronic kidney disease. Nat Genet 42 373 5
19. MaRCTamCHWangYLukAOHuC 2010 Genetic variants of the protein kinase C-beta 1 gene and development of end-stage renal disease in patients with type 2 diabetes. JAMA 304 881 9
20. ShimazakiAKawamuraYKanazawaASekineASaitoS 2005 Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. Diabetes 54 1171 8
21. PezzolesiMGKatavetinPKureMPoznikGDSkupienJ 2009 Confirmation of genetic associations at ELMO1 in the GoKinD collection supports its role as a susceptibility gene in diabetic nephropathy. Diabetes 58 2698 702
22. PezzolesiMGPoznikGDMychaleckyjJCPatersonADBaratiMT 2009 Genome-wide association scan for diabetic nephropathy susceptibility genes in type 1 diabetes. Diabetes 58 1403 10
23. AlkhalafABakkerSJBiloHJGansRONavisGJ A polymorphism in the gene encoding carnosinase (CNDP1) as a predictor of mortality and progression from nephropathy to end-stage renal disease in type 1 diabetes mellitus. Diabetologia 53 2562 8
24. FreedmanBIBostromMDaeihaghPBowdenDW 2007 Genetic factors in diabetic nephropathy. Clin J Am Soc Nephrol 2 1306 16
25. HeBOsterholmAMHoverfaltAForsblomCHjorleifsdottirEE 2009 Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. Am J Hum Genet 84 5 13
26. ZhangDEfendicSBrismarK Gu HF Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus. BMC Med Genet 11 116
27. KöttgenAHwangSJRampersaudECoreshJNorthKE 2008 TCF7L2 variants associate with CKD progression and renal function in population-based cohorts. J Am Soc Nephrol 19 1989 99
28. LiuMShiSSenthilnathanSYuJWuE 2010 Genetic variation of DKK3 may modify renal disease severity in ADPKD. J Am Soc Nephrol 21 1510 20
29. WheelerHEMetterEJTanakaTAbsherDHigginsJ 2009 Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging. PLoS Genet 5 e1000685 doi:10.1371/journal.pgen.1000685
30. BrancatiFLWheltonPKRandallBLNeatonJDStamlerJ 1997 Risk of end-stage renal disease in diabetes mellitus: a prospective cohort study of men screened for MRFIT. Multiple Risk Factor Intervention Trial. JAMA 278 2069 74
31. 2002 K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39 S1 266
32. BashLDAstorBCCoreshJ 2010 Risk of incident ESRD: a comprehensive look at cardiovascular risk factors and 17 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis 55 31 41
33. KronenbergF 2009 Emerging risk factors and markers of chronic kidney disease progression. Nat Rev Nephrol 5 677 89
34. PilleboutEBurtinMYuanHTBriandPWoolfAS 2001 Proliferation and remodeling of the peritubular microcirculation after nephron reduction: association with the progression of renal lesions. Am J Pathol 159 547 60
35. ViauAEl KarouiKLaouariDBurtinMNguyenC 2010 Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J Clin Invest 120 4065 76
36. SchmidHBoucherotAYasudaYHengerABrunnerB 2006 Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes 55 2993 3003
37. Al-AlyZZeringueAFuJRauchmanMIMcDonaldJR 2010 Rate of Kidney Function Decline Associates with Mortality. J Am Soc Nephrol 21 1961 9
38. DalrympleLSKatzRKestenbaumBShlipakMGSarnakMJ 2011 Chronic Kidney Disease and the Risk of End-Stage Renal Disease versus Death. J Gen Intern Med 26 379 85
39. AgarwalRBunayeZBekeleDMLightRP 2008 Competing risk factor analysis of end-stage renal disease and mortality in chronic kidney disease. Am J Nephrol 28 569 75
40. BorthwickEFergusonA Perioperative acute kidney injury: risk factors, recognition, management, and outcomes. BMJ 341 c3365
41. KellyKJDominguezJH Rapid Progression of Diabetic Nephropathy Is Linked to Inflammation and Episodes of Acute Renal Failure. Am J Nephrol 32 469 75
42. van KuijkJPFluWJChoncholMHoeksSEWinkelTA 2010 Temporary perioperative decline of renal function is an independent predictor for chronic kidney disease. Clin J Am Soc Nephrol 5 1198 204
43. JamesMTGhaliWATonelliMFarisPKnudtsonML Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function. Kidney Int 78 803 9
44. RoncoCMcCulloughPAAnkerSDAnandIAspromonteN Cardiorenal syndromes: an executive summary from the consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol 165 54 67
45. WinkelmayerWCOwenWFJrLevinRAvornJ 2003 A propensity analysis of late versus early nephrologist referral and mortality on dialysis. J Am Soc Nephrol 14 486 92
46. WardMM 2009 Access to care and the incidence of end-stage renal disease due to diabetes. Diabetes Care 32 1032 6
47. SoderlandPLovekarSWeinerDEBrooksDRKaufmanJS Chronic kidney disease associated with environmental toxins and exposures. Adv Chronic Kidney Dis 17 254 64
48. MannJFSchmiederREMcQueenMDyalLSchumacherH 2008 Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 372 547 53
49. LeveyASCoreshJGreeneTStevensLAZhangYL 2006 Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145 247 54
50. WillerCJLiYAbecasisGR METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26 2190 1
51. DerSimonianRLairdN 1986 Meta-analysis in clinical trials. Control Clin Trials 7 177 88
52. GaudermanWJ 2002 Sample size requirements for matched case-control studies of gene-environment interaction. Stat Med 21 35 50
53. JohnsonADHandsakerREPulitSLNizzariMMO'DonnellCJ 2008 SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 24 2938 9
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 9
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