Skip to main content

Advertisement

Log in

Genetic susceptibility to hypertensive renal disease

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Hypertensive renal disease occurs at increased frequency among the relatives of patients with this disease compared to individuals who lack a family history of disease. This suggests a heritable risk in which genetic variation may play a role. These observations have motivated a search for genetic variation contributing to this risk in both experimental animal models and in human populations. Studies of animal models indicate the capacity of natural genetic variants to contribute to disease risk and have produced a few insights into the disease mechanism. In its current phase, human population genetic studies have sought to associate genetic variation with disease in large populations by testing genotypes at a large number of common genetic variations in the genome, expecting that common genetic variants contributing to renal disease risk will be identified. These genome-wide association studies (GWAS) have been productive and are a clear technical success; they have also identified narrowly defined loci and genes containing variation contributing to disease risk. Further extension and refinement of these GWAS are likely to extend this success. However, it is also clear that few additional variants with substantial effects accounting for the greatest part of heritability will be uncovered by GWAS. This raises an interesting biological question regarding where the remaining unaccounted heritable risk may be located. At present, much consideration is being given to this question and to the challenge of testing hypotheses that lead from the various alternative mechanisms under consideration. One result of the progress of GWAS is likely to be a renewed interest in mechanisms by which related individuals can share and transmit traits independently of Mendelian inheritance. This paper reviews the current progress in this area and considers other mechanisms by which familial aggregation of risk for renal disease may arise.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AA:

African American

eGFR:

Estimated glomerular filtration rate

ESRD:

End-stage renal disease

GWAS:

Genome-wide association study

SHR:

Spontaneously hypertensive rat

SNP:

Single-nucleotide polymorphism

References

  1. Collins AJ Unites States Renal Data System, Annual Report 2011. http://www.usrds.org/

  2. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT (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(9731):2073–2081

    Article  PubMed  Google Scholar 

  3. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351(13):1296–1305

    Article  PubMed  CAS  Google Scholar 

  4. Freedman BI (2003) Susceptibility genes for hypertension and renal failure. J Am Soc Nephrol 14(7 Suppl 2):S192–S194

    Article  PubMed  CAS  Google Scholar 

  5. Freedman BI, Spray BJ, Tuttle AB, Buckalew VM Jr (1993) The familial risk of end-stage renal disease in African Americans. Am J Kidney Dis 21(4):387–393

    PubMed  CAS  Google Scholar 

  6. Freedman BI, Soucie JM, McClellan WM (1997) Family history of end-stage renal disease among incident dialysis patients. J Am Soc Nephrol 8(12):1942–1945

    PubMed  CAS  Google Scholar 

  7. Lei HH, Perneger TV, Klag MJ, Whelton PK, Coresh J (1998) Familial aggregation of renal disease in a population-based case-control study. J Am Soc Nephrol 9(7):1270–1276

    PubMed  CAS  Google Scholar 

  8. Spray BJ, Atassi NG, Tuttle AB, Freedman BI (1995) Familial risk, age at onset, and cause of end-stage renal disease in white Americans. J Am Soc Nephrol 5(10):1806–1810

    PubMed  CAS  Google Scholar 

  9. Yazbek SN, Spiezio SH, Nadeau JH, Buchner DA (2010) Ancestral paternal genotype controls body weight and food intake for multiple generations. Hum Mol Genet 19(21):4134–4144

    Article  PubMed  CAS  Google Scholar 

  10. Freedman BI, Tuttle AB, Spray BJ (1995) Familial predisposition to nephropathy in African Americans with non-insulin-dependent diabetes mellitus. Am J Kidney Dis 25(5):710–713

    Article  PubMed  CAS  Google Scholar 

  11. Faronato PP, Maioli M, Tonolo G, Brocco E, Noventa F, Piarulli F, Abaterusso C, Modena F, de Bigontina G, Velussi M, Inchiostro S, Santeusanio F, Bueti A, Nosadini R (1997) Clustering of albumin excretion rate abnormalities in Caucasian patients with NIDDM. The Italian NIDDM Nephropathy Study Group. Diabetologia 40(7):816–823

    Article  PubMed  CAS  Google Scholar 

  12. Brown DM, Provoost AP, Daly MJ, Lander ES, Jacob HJ (1996) Renal disease susceptibility and hypertension are under independent genetic control in the fawn-hooded rat. Nat Genet 12(1):44–51

    Article  PubMed  CAS  Google Scholar 

  13. Gigante B, Rubattu S, Stanzione R, Lombardi A, Baldi A, Baldi F, Volpe M (2003) Contribution of genetic factors to renal lesions in the stroke-prone spontaneously hypertensive rat. Hypertension 42(4):702–706

    Article  PubMed  CAS  Google Scholar 

  14. Bell R, Herring SM, Gokul N, Monita M, Grove ML, Boerwinkle E, Doris PA (2011) High-resolution identity by descent mapping uncovers the genetic basis for blood pressure differences between SHR lines. Circ Cardiovasc Genet 4(3):223–231

    Article  PubMed  CAS  Google Scholar 

  15. Schelling JR, Zarif L, Sehgal A, Iyengar S, Sedor JR (1999) Genetic susceptibility to end-stage renal disease. Curr Opin Nephrol Hypertens 8(4):465–472

    Article  PubMed  CAS  Google Scholar 

  16. DeWan AT, Arnett DK, Atwood LD, Province MA, Lewis CE, Hunt SC, Eckfeldt J (2001) A genome scan for renal function among hypertensives: the HyperGEN study. Am J Hum Genet 68(1):136–144

    Article  PubMed  CAS  Google Scholar 

  17. Freedman BI, Beck SR, Rich SS, Heiss G, Lewis CE, Turner S, Province MA, Schwander KL, Arnett DK, Mellen BG (2003) A genome-wide scan for urinary albumin excretion in hypertensive families. Hypertension 42(3):291–296

    Article  PubMed  CAS  Google Scholar 

  18. Fox CS, Yang Q, Guo CY, Cupples LA, Wilson PW, Levy D, Meigs JB (2005) Genome-wide linkage analysis to urinary microalbuminuria in a community-based sample: the Framingham Heart Study. Kidney Int 67(1):70–74

    Article  PubMed  Google Scholar 

  19. Leon JM, Freedman BI, Miller MB, North KE, Hunt SC, Eckfeldt JH, Lewis CE, Kraja AT, Djousse L, Arnett DK (2007) Genome scan of glomerular filtration rate and albuminuria: the HyperGEN study. Nephrol Dial Transplant 22(3):763–771

    Article  PubMed  CAS  Google Scholar 

  20. Arar N, Nath S, Thameem F, Bauer R, Voruganti S, Comuzzie A, Cole S, Blangero J, MacCluer J, Abboud H (2007) Genome-wide scans for microalbuminuria in Mexican Americans: the San Antonio Family Heart Study. Genet Med 9(2):80–87

    Article  PubMed  CAS  Google Scholar 

  21. Anderson CA, Pettersson FH, Barrett JC, Zhuang JJ, Ragoussis J, Cardon LR, Morris AP (2008) Evaluating the effects of imputation on the power, coverage, and cost efficiency of genome-wide SNP platforms. Am J Hum Genet 83(1):112–119

    Article  PubMed  CAS  Google Scholar 

  22. Balding DJ (2006) A tutorial on statistical methods for population association studies. Nat Rev Genet 7(10):781–791

    Article  PubMed  CAS  Google Scholar 

  23. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, Smith AV, Tobin MD, Verwoert GC, Hwang SJ, Pihur V, Vollenweider P, O’Reilly PF, Amin N, Bragg-Gresham JL, Teumer A, Glazer NL, Launer L, Hua Zhao J, Aulchenko Y, Heath S, Sober S, Parsa A, Luan J, Arora P, Dehghan A, Zhang F, Lucas G, Hicks AA, Jackson AU, Peden JF, Tanaka T, Wild SH, Rudan I, Igl W, Milaneschi Y, Parker AN, Fava C, Chambers JC, Fox ER, Kumari M, Jin Go M, van der Harst P, Hong Linda Kao W, Sjogren M, Vinay DG, Alexander M, Tabara Y, Shaw-Hawkins S, Whincup PH, Liu Y, Shi G, Kuusisto J, Tayo B, Seielstad M, Sim X, Hoang Nguyen KD, Lehtimaki T, Matullo G, Wu Y, Gaunt TR, Charlotte Onland-Moret N, Cooper MN, Platou CG, Org E, Hardy R, Dahgam S, Palmen J, Vitart V, Braund PS, Kuznetsova T, Uiterwaal CS, Adeyemo A, Palmas W, Campbell H, Ludwig B, Tomaszewski M, Tzoulaki I, Palmer ND, Aspelund T, Garcia M, Chang YP, O’Connell JR, Steinle NI, Grobbee DE, Arking DE, Kardia SL, Morrison AC, Hernandez D, Najjar S, McArdle WL, Hadley D, Brown MJ, Connell JM, Hingorani AD, Day IN, Lawlor DA, Beilby JP, Lawrence RW, Clarke R, Hopewell JC, Ongen H, Dreisbach AW, Li Y, Hunter Young J, Bis JC, Kahonen M, Viikari J, Adair LS, Lee NR, Chen MH, Olden M, Pattaro C, Hoffman Bolton JA, Kottgen A, Bergmann S, Mooser V, Chaturvedi N, Frayling TM, Islam M, Jafar TH, Erdmann J, Kulkarni SR, Bornstein SR, Grassler J, Groop L, Voight BF, Kettunen J, Howard P, Taylor A, Guarrera S, Ricceri F, Emilsson V, Plump A, Barroso I, Khaw KT, Weder AB, Hunt SC, Sun YV, Bergman RN, Collins FS, Bonnycastle LL, Scott LJ, Stringham HM, Peltonen L, Perola M, Vartiainen E, Brand SM, Staessen JA, Wang TJ, Burton PR, Soler Artigas M, Dong Y, Snieder H, Wang X, Zhu H, Lohman KK, Rudock ME, Heckbert SR, Smith NL, Wiggins KL, Doumatey A, Shriner D, Veldre G, Viigimaa M, Kinra S, Prabhakaran D, Tripathy V, Langefeld CD, Rosengren A, Thelle DS, Maria Corsi A, Singleton A, Forrester T, Hilton G, McKenzie CA, Salako T, Iwai N, Kita Y, Ogihara T, Ohkubo T, Okamura T, Ueshima H, Umemura S, Eyheramendy S, Meitinger T, Wichmann HE, Shin Cho Y, Kim HL, Lee JY, Scott J, Sehmi JS, Zhang W, Hedblad B, Nilsson P, Davey Smith G, Wong A, Narisu N, Stancakova A, Raffel LJ, Yao J, Kathiresan S, O’Donnell CJ, Schwartz SM, Arfan Ikram M, Longstreth Jr WT, Mosley TH, Seshadri S, Shrine NR, Wain LV, Morken MA, Swift AJ, Laitinen J, Prokopenko I, Zitting P, Cooper JA, Humphries SE, Danesh J, Rasheed A, Goel A, Hamsten A, Watkins H, Bakker SJ, van Gilst WH, Janipalli CS, Radha Mani K, Yajnik CS, Hofman A, Mattace-Raso FU, Oostra BA, Demirkan A, Isaacs A, Rivadeneira F, Lakatta EG, Orru M, Scuteri A, Ala-Korpela M, Kangas AJ, Lyytikainen LP, Soininen P, Tukiainen T, Wurtz P, Twee-Hee Ong R, Dorr M, Kroemer HK, Volker U, Volzke H, Galan P, Hercberg S, Lathrop M, Zelenika D, Deloukas P, Mangino M, Spector TD, Zhai G, Meschia JF, Nalls MA, Sharma P, Terzic J, Kranthi Kumar MV, Denniff M, Zukowska-Szczechowska E, Wagenknecht LE, Gerald RFF, Charchar FJ, Schwarz PE, Hayward C, Guo X, Rotimi C, Bots ML, Brand E, Samani NJ, Polasek O, Talmud PJ, Nyberg F, Kuh D, Laan M, Hveem K, Palmer LJ, van der Schouw YT, Casas JP, Mohlke KL, Vineis P, Raitakari O, Ganesh SK, Wong TY, Shyong Tai E, Cooper RS, Laakso M, Rao DC, Harris TB, Morris RW, Dominiczak AF, Kivimaki M, Marmot MG, Miki T, Saleheen D, Chandak GR, Coresh J, Navis G, Salomaa V, Han BG, Zhu X, Kooner JS, Melander O, Ridker PM, Bandinelli S, Gyllensten UB, Wright AF, Wilson JF, Ferrucci L, Farrall M, Tuomilehto J, Pramstaller PP, Elosua R, Soranzo N, Sijbrands EJ, Altshuler D, Loos RJ, Shuldiner AR, Gieger C, Meneton P, Uitterlinden AG, Wareham NJ, Gudnason V, Rotter JI, Rettig R, Uda M, Strachan DP, Witteman JC, Hartikainen AL, Beckmann JS, Boerwinkle E, Vasan RS, Boehnke M, Larson MG, Jarvelin MR, Psaty BM, Abecasis GR, Chakravarti A, Elliott P, van Duijn CM, Newton-Cheh C, Levy D, Caulfield MJ, Johnson T (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478:103–109

  24. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678

    Google Scholar 

  25. Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Ferrucci L, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Marechal C, Melander O, Munroe PB, Nordfors L, Parsa A, Peltonen L, Penninx BW, Perucha E, Pouta A, Prokopenko I, Roderick PJ, Ruokonen A, Samani NJ, Sanna S, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Shuldiner AR, Sjogren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Tanaka T, Ubink-Veltmaat LJ, Uda M, Vollenweider P, Wallace C, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Mooser V, Abecasis GR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JS (2010) Genetic loci influencing kidney function and chronic kidney disease. Nat Genet 42(5):373–375

  26. Kottgen A, Glazer NL, Dehghan A, Hwang SJ, Katz R, Li M, Yang Q, Gudnason V, Launer LJ, Harris TB, Smith AV, Arking DE, Astor BC, Boerwinkle E, Ehret GB, Ruczinski I, Scharpf RB, Chen YD, de Boer IH, Haritunians T, Lumley T, Sarnak M, Siscovick D, Benjamin EJ, Levy D, Upadhyay A, Aulchenko YS, Hofman A, Rivadeneira F, Uitterlinden AG, van Duijn CM, Chasman DI, Pare G, Ridker PM, Kao WH, Witteman JC, Coresh J, Shlipak MG, Fox CS (2009) Multiple loci associated with indices of renal function and chronic kidney disease. Nat Genet 41(6):712–717

    Article  PubMed  CAS  Google Scholar 

  27. Kottgen A, Pattaro C, Boger CA, Fuchsberger C, Olden M, Glazer NL, Parsa A, Gao X, Yang Q, Smith AV, O’Connell JR, Li M, Schmidt H, Tanaka T, Isaacs A, Ketkar S, Hwang SJ, Johnson AD, Dehghan A, Teumer A, Pare G, Atkinson EJ, Zeller T, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tonjes A, Hayward C, Aspelund T, Eiriksdottir G, Launer LJ, Harris TB, Rampersaud E, Mitchell BD, Arking DE, Boerwinkle E, Struchalin M, Cavalieri M, Singleton A, Giallauria F, Metter J, de Boer IH, Haritunians T, Lumley T, Siscovick D, Psaty BM, Zillikens MC, Oostra BA, Feitosa M, Province M, de Andrade M, Turner ST, Schillert A, Ziegler A, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Illig T, Klopp N, Meisinger C, Wichmann HE, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Schreiber S, Aulchenko YS, Felix JF, Rivadeneira F, Uitterlinden AG, Hofman A, Imboden M, Nitsch D, Brandstatter A, Kollerits B, Kedenko L, Magi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Volzke H, Kroemer HK, Nauck M, Volker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Blankenberg S, Liu Y, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Gudnason V, Shuldiner AR, Coresh J, Schmidt R, Ferrucci L, Shlipak MG, van Duijn CM, Borecki I, Kramer BK, Rudan I, Gyllensten U, Wilson JF, Witteman JC, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS (2010) New loci associated with kidney function and chronic kidney disease. Nat Genet 42(5):376–384

    Article  PubMed  Google Scholar 

  28. Pattaro C, De Grandi A, Vitart V, Hayward C, Franke A, Aulchenko YS, Johansson A, Wild SH, Melville SA, Isaacs A, Polasek O, Ellinghaus D, Kolcic I, Nothlings U, Zgaga L, Zemunik T, Gnewuch C, Schreiber S, Campbell S, Hastie N, Boban M, Meitinger T, Oostra BA, Riegler P, Minelli C, Wright AF, Campbell H, van Duijn CM, Gyllensten U, Wilson JF, Krawczak M, Rudan I, Pramstaller PP (2010) A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level. BMC Med Genet 11:41

    Article  PubMed  Google Scholar 

  29. Kottgen A (2010) Genome-wide association studies in nephrology research. Am J Kidney Dis 56(4):743–758

    Article  PubMed  Google Scholar 

  30. Sheikh-Hamad D (2010) Mammalian stanniocalcin-1 activates mitochondrial antioxidant pathways: new paradigms for regulation of macrophages and endothelium. Am J Physiol Renal Physiol 298(2):F248–F254

    Article  PubMed  CAS  Google Scholar 

  31. Wang Y, Huang L, Abdelrahim M, Cai Q, Truong A, Bick R, Poindexter B, Sheikh-Hamad D (2009) Stanniocalcin-1 suppresses superoxide generation in macrophages through induction of mitochondrial UCP2. J Leukoc Biol 86(4):981–988

    Article  PubMed  CAS  Google Scholar 

  32. Saemann MD, Weichhart T, Zeyda M, Staffler G, Schunn M, Stuhlmeier KM, Sobanov Y, Stulnig TM, Akira S, von Gabain A, von Ahsen U, Horl WH, Zlabinger GJ (2005) Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4-dependent mechanism. J Clin Invest 115(2):468–475

    PubMed  Google Scholar 

  33. Kottgen A, Hwang SJ, Larson MG, Van Eyk JE, Fu Q, Benjamin EJ, Dehghan A, Glazer NL, Kao WH, Harris TB, Gudnason V, Shlipak MG, Yang Q, Coresh J, Levy D, Fox CS (2010) Uromodulin levels associate with a common UMOD variant and risk for incident CKD. J Am Soc Nephrol 21(2):337–344

    Article  PubMed  CAS  Google Scholar 

  34. Padmanabhan S, Melander O, Johnson T, Di Blasio AM, Lee WK, Gentilini D, Hastie CE, Menni C, Monti MC, Delles C, Laing S, Corso B, Navis G, Kwakernaak AJ, van der Harst P, Bochud M, Maillard M, Burnier M, Hedner T, Kjeldsen S, Wahlstrand B, Sjogren M, Fava C, Montagnana M, Danese E, Torffvit O, Hedblad B, Snieder H, Connell JM, Brown M, Samani NJ, Farrall M, Cesana G, Mancia G, Signorini S, Grassi G, Eyheramendy S, Wichmann HE, Laan M, Strachan DP, Sever P, Shields DC, Stanton A, Vollenweider P, Teumer A, Volzke H, Rettig R, Newton-Cheh C, Arora P, Zhang F, Soranzo N, Spector TD, Lucas G, Kathiresan S, Siscovick DS, Luan J, Loos RJ, Wareham NJ, Penninx BW, Nolte IM, McBride M, Miller WH, Nicklin SA, Baker AH, Graham D, McDonald RA, Pell JP, Sattar N, Welsh P, Munroe P, Caulfield MJ, Zanchetti A, Dominiczak AF (2010) Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension. PLoS Genet 6(10):e1001177

    Article  PubMed  Google Scholar 

  35. Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BE, Breteler MM, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PT, van Duijn CM, Kao L, Cheng CY, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T, Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, Macgregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FM, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TY (2010) Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. PLoS Genet 6(10):e1001184

    Article  PubMed  Google Scholar 

  36. Turner ST, Kardia SL, Mosley TH, Rule AD, Boerwinkle E, de Andrade M (2006) Influence of genomic loci on measures of chronic kidney disease in hypertensive sibships. J Am Soc Nephrol 17(7):2048–2055

    Article  PubMed  CAS  Google Scholar 

  37. Chakraborty R, Weiss KM (1988) Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci. Proc Nat Acad Sci 85(23):9119–9123

    Article  PubMed  CAS  Google Scholar 

  38. Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, Coresh J, Patterson N, Tandon A, Powe NR, Fink NE, Sadler JH, Weir MR, Abboud HE, Adler SG, Divers J, Iyengar SK, Freedman BI, Kimmel PL, Knowler WC, Kohn OF, Kramp K, Leehey DJ, Nicholas SB, Pahl MV, Schelling JR, Sedor JR, Thornley-Brown D, Winkler CA, Smith MW, Parekh RS (2008) MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40(10):1185–1192

    Article  PubMed  CAS  Google Scholar 

  39. Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, Oleksyk T, McKenzie LM, Kajiyama H, Ahuja TS, Berns JS, Briggs W, Cho ME, Dart RA, Kimmel PL, Korbet SM, Michel DM, Mokrzycki MH, Schelling JR, Simon E, Trachtman H, Vlahov D, Winkler CA (2008) MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 40(10):1175–1184

    Article  PubMed  CAS  Google Scholar 

  40. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329(5993):841–845

    Google Scholar 

  41. Pollak MR (2008) Kidney disease and African ancestry. Nat Genet 40(10):1145–1146

    Article  PubMed  CAS  Google Scholar 

  42. Seri M, Pecci A, Di Bari F, Cusano R, Savino M, Panza E, Nigro A, Noris P, Gangarossa S, Rocca B, Gresele P, Bizzaro N, Malatesta P, Koivisto PA, Longo I, Musso R, Pecoraro C, Iolascon A, Magrini U, Rodriguez Soriano J, Renieri A, Ghiggeri GM, Ravazzolo R, Balduini CL, Savoia A (2003) MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine 82(3):203–215

    Google Scholar 

  43. Ghiggeri GM, Caridi G, Magrini U, Sessa A, Savoia A, Seri M, Pecci A, Romagnoli R, Gangarossa S, Noris P, Sartore S, Necchi V, Ravazzolo R, Balduini CL (2003) Genetics, clinical and pathological features of glomerulonephritis associated with mutations of nonmuscle myosin IIA (Fechtner syndrome). Am J Kidney Dis 41(1):95–104

    Article  PubMed  CAS  Google Scholar 

  44. Johnstone DB, Zhang J, George B, Leon C, Gachet C, Wong H, Parekh R, Holzman LB (2011) Podocyte-specific deletion of Myh9 encoding nonmuscle myosin heavy chain 2A predisposes mice to glomerulopathy. Mol Cell Biol 31(10):2162–2170

    Article  PubMed  CAS  Google Scholar 

  45. Tzur S, Rosset S, Shemer R, Yudkovsky G, Selig S, Tarekegn A, Bekele E, Bradman N, Wasser WG, Behar DM, Skorecki K (2010) Missense mutations in the APOL1 gene are highly associated with end-stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet 128(3):345–350

    Article  PubMed  CAS  Google Scholar 

  46. Zuk O, Hechter E, Sunyaev SR, Lander ES (2012) The mystery of missing heritability: genetic interactions create phantom heritability. Proc Nat Acad Sci (in press) PMID: 22223662

  47. Shao H, Burrage LC, Sinasac DS, Hill AE, Ernest SR, O’Brien W, Courtland HW, Jepsen KJ, Kirby A, Kulbokas EJ, Daly MJ, Broman KW, Lander ES, Nadeau JH (2008) Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. Proc Natl Acad Sci USA 105(50):19910–19914

    Article  PubMed  CAS  Google Scholar 

  48. Crow JF (2010) On epistasis: why it is unimportant in polygenic directional selection. Philos Trans R Soc Lond B Biol Sci 365(1544):1241–1244

    Article  PubMed  Google Scholar 

  49. Van Dijk SJ, Specht PA, Lazar J, Jacob HJ, Provoost AP (2006) Synergistic QTL interactions between Rf-1 and Rf-3 increase renal damage susceptibility in double congenic rats. Kidney Int 69(8):1369–1376

    PubMed  Google Scholar 

  50. Das R, Hampton DD, Jirtle RL (2009) Imprinting evolution and human health. Mamm Genome 20(9–10):563–572

    Article  PubMed  Google Scholar 

  51. Moore T, Haig D (1991) Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet 7(2):45–49

    Article  PubMed  CAS  Google Scholar 

  52. Kucharski R, Maleszka J, Foret S, Maleszka R (2008) Nutritional control of reproductive status in honeybees via DNA methylation. Science 319(5871):1827–1830

    Article  PubMed  CAS  Google Scholar 

  53. Nelson VR, Spiezio SH, Nadeau JH (2010) Transgenerational genetic effects of the paternal Y chromosome on daughters’ phenotypes. Epigenomics 2(4):513–521

    Article  PubMed  CAS  Google Scholar 

  54. Dunn GA, Bale TL (2011) Maternal high-fat diet effects on third-generation female body size via the paternal lineage. Endocrinology 152(6):2228–2236

    Article  PubMed  CAS  Google Scholar 

  55. Grindstaff JL, Hasselquist D, Nilsson JK, Sandell M, Smith HG, Stjernman M (2006) Transgenerational priming of immunity: maternal exposure to a bacterial antigen enhances offspring humoral immunity. Proc Biol Sci 273(1600):2551–2557

    Article  PubMed  CAS  Google Scholar 

  56. Hasselquist D, Nilsson JA (2009) Maternal transfer of antibodies in vertebrates: trans-generational effects on offspring immunity. Philos Trans R Soc Lond B Biol Sci 364(1513):51–60

    Article  PubMed  Google Scholar 

  57. Reid JM, Arcese P, Keller LF, Hasselquist D (2006) Long-term maternal effect on offspring immune response in song sparrows Melospiza melodia. Biol Lett 2(4):573–576

    Article  PubMed  Google Scholar 

  58. Sadd BM, Kleinlogel Y, Schmid-Hempel R, Schmid-Hempel P (2005) Trans-generational immune priming in a social insect. Biol Lett 1(4):386–388

    Article  PubMed  Google Scholar 

  59. Greeley SA, Katsumata M, Yu L, Eisenbarth GS, Moore DJ, Goodarzi H, Barker CF, Naji A, Noorchashm H (2002) Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice. Nat Med 8(4):399–402

    Article  PubMed  CAS  Google Scholar 

  60. Yamashita T, Freigang S, Eberle C, Pattison J, Gupta S, Napoli C, Palinski W (2006) Maternal immunization programs postnatal immune responses and reduces atherosclerosis in offspring. Circ Res 99(7):e51–e64

    Article  PubMed  CAS  Google Scholar 

  61. Lundin BS, Dahlman-Hoglund A, Pettersson I, Dahlgren UI, Hanson LA, Telemo E (1999) Antibodies given orally in the neonatal period can affect the immune response for two generations: evidence for active maternal influence on the newborn’s immune system. Scand J Immunol 50(6):651–656

    Article  PubMed  CAS  Google Scholar 

  62. Matson AP, Thrall RS, Rafti E, Puddington L (2009) Breastmilk from allergic mothers can protect offspring from allergic airway inflammation. Breastfeeding Med 4(3):167–174

    Article  Google Scholar 

  63. Polte T, Hansen G (2008) Maternal tolerance achieved during pregnancy is transferred to the offspring via breast milk and persistently protects the offspring from allergic asthma. Clin Exp Allergy 38(12):1950–1958

    Article  PubMed  CAS  Google Scholar 

  64. Lange H, Kiesch B, Linden I, Otto M, Thierse HJ, Shaw L, Maehnss K, Hansen H, Lemke H (2002) Reversal of the adult IgE high responder phenotype in mice by maternally transferred allergen-specific monoclonal IgG antibodies during a sensitive period in early ontogeny. Eur J Immunol 32(11):3133–3141

    Article  PubMed  CAS  Google Scholar 

  65. Jerne NK (1985) The generative grammar of the immune system. Science 229(4718):1057–1059

    Article  PubMed  CAS  Google Scholar 

  66. Lefranc MP, Clement O, Kaas Q, Duprat E, Chastellan P, Coelho I, Combres K, Ginestoux C, Giudicelli V, Chaume D, Lefranc G (2005) IMGT-Choreography for immunogenetics and immunoinformatics. In Silico Biol 5(1):45–60

    PubMed  CAS  Google Scholar 

  67. Teng G, Papavasiliou FN (2007) Immunoglobulin somatic hypermutation. Annu Rev Genet 41:107–120

    Article  PubMed  CAS  Google Scholar 

  68. Hopkin J, Cookson W (2006) Genetic variation in the beta subunit of the high affinity IgE receptor and atopy and asthma. Clin Exp Allergy 36(7):855–857

    Article  PubMed  CAS  Google Scholar 

  69. Weidinger S, Gieger C, Rodriguez E, Baurecht H, Mempel M, Klopp N, Gohlke H, Wagenpfeil S, Ollert M, Ring J, Behrendt H, Heinrich J, Novak N, Bieber T, Kramer U, Berdel D, von Berg A, Bauer CP, Herbarth O, Koletzko S, Prokisch H, Mehta D, Meitinger T, Depner M, von Mutius E, Liang L, Moffatt M, Cookson W, Kabesch M, Wichmann HE, Illig T (2008) Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genet 4(8):e1000166

    Article  PubMed  Google Scholar 

  70. Cierpial MA, McCarty R (1987) Hypertension in SHR rats: contribution of maternal environment. Am J Physiol 253(4 Pt 2):H980–H984

    PubMed  CAS  Google Scholar 

  71. Di Nicolantonio R, Koutsis K, Westcott KT, Wlodek ME (2006) Relative contribution of the prenatal versus postnatal period on development of hypertension and growth rate of the spontaneously hypertensive rat. Clin Exp Pharmacol Physiol 33(1–2):9–16

    Article  PubMed  Google Scholar 

  72. Lee JY, Azar SH (2010) Wistar-Kyoto and spontaneously hypertensive rat blood pressure after embryo transfer into different wombs and cross-suckling. Exp Biol Med (Maywood) 235(11):1375–1384

    Article  CAS  Google Scholar 

  73. Herring SM, Gokul N, Monita M, Bell R, Boerwinkle E, Wenderfer SE, Braun MC, Doris PA (2011) Immunoglobulin locus associates with serum IgG levels and albuminuria. J Am Soc Nephrol 22(5):881–889

    Article  PubMed  CAS  Google Scholar 

  74. Oxelius VA (2008) Immunoglobulin constant heavy G subclass chain genes in asthma and allergy. Immunol Res 40(2):179–191

    Article  PubMed  CAS  Google Scholar 

  75. Puttick AH, Briggs DC, Welsh KI, Williamson EA, Jacoby RK, Jones VE (1990) Genes associated with rheumatoid arthritis and mild inflammatory arthritis. II. Association of HLA with complement C3 and immunoglobulin Gm allotypes. Ann Rheum Dis 49(4):225–228

    Article  PubMed  CAS  Google Scholar 

  76. Schernthaner G, Mayr WR (1984) Immunoglobulin allotype markers and HLA DR genes in type I diabetes mellitus. Metabolism 33(9):833–836

    Article  PubMed  CAS  Google Scholar 

  77. Field LL (1991) Non-HLA region genes in insulin dependent diabetes mellitus. Baillieres Clin Endocrinol Metab 5(3):413–438

    Article  PubMed  CAS  Google Scholar 

  78. Field LL, Stephure DK, McArthur RG (1991) Interaction between T cell receptor beta chain and immunoglobulin heavy chain region genes in susceptibility to insulin-dependent diabetes mellitus. Am J Hum Genet 49(3):627–634

    PubMed  CAS  Google Scholar 

  79. Pandey JP (2010) Genome-wide association studies and assessment of risk of disease. N Engl J Med 363(21):2076–2077

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The author is grateful to Stacy Herring for technical assistance and for the following research grants NIH R01 DK069632 (to PAD) R01 DK081866 (to PAD) and AHA 09GRNT2240045 (to PAD).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter A. Doris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doris, P.A. Genetic susceptibility to hypertensive renal disease. Cell. Mol. Life Sci. 69, 3751–3763 (2012). https://doi.org/10.1007/s00018-012-0996-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-012-0996-3

Keywords

Navigation