Skip to main content
SpringerLink
Log in

Molekulargenetik der humanen Hypertonie

Molecular genetics of human hypertension

  • Schwerpunkt: Hypertonie
  • Published:
Der Internist Aims and scope Submit manuscript

Zusammenfassung

Vor über 100 Jahren wurde ein genetischer Einfluss auf den Blutdruck nachgewiesen und ein einfacher Erbgang gemäß den Mendel-Regeln vermutet. Platt und Pickering führten eine lebhafte Debatte über dieses Thema. Platt favorisierte die Idee, dass ein einzelnes Gen oder nur wenige Gene für den Bluthochdruck verantwortlich seien. Pickering legte Forschungsergebnisse vor, die vermuten ließen, dass viele Gene Einfluss auf den Blutdruck ausüben. Dies alles in einer Zeit, in der man noch nicht wusste, was Gene überhaupt sind. Genomweite Assoziationsstudien (GWAS) nach dem Pickering-Modell weisen auf > 500 blutdruckrelevante Genloci hin, die über das gesamte Genom verteilt sind. Jedes einzelne Gen übt nur einen kleinen Einfluss auf den Blutdruck aus. Als Außenseiter der Hochdruckforschung gelten sekundäre Ursachen. Bei Phäochromozytom, Aldosteronismus, Cushing-Syndrom und sogar bei der fibromuskulären Dysplasie (renovaskuläre Hypertonie) lassen die Ergebnisse darauf schließen, dass der sekundären Hypertonie regelmäßig eine genetische Ursache zugrunde liegt. Damit wurde auch die Theorie von Platt teilweise bestätigt. Mittlerweile wurde eine Vielzahl von Hypertonieformen mit einem genetischen Erbgang nach Mendel beschrieben. Jede dieser Genvarianten übt einen beträchtlichen Einfluss auf den Blutdruck aus. Eine Vielzahl neuer physiologischer Mechanismen wurde dadurch aufgeklärt. Diese Befunde werden therapeutische Bedeutung haben. Also obliegt es den Klinikern, über diese Forschungsergebnisse bestens informiert zu sein.

Abstract

A genetic influence on blood pressure was demonstrated more than 100 years ago and a simple Mendelian inheritance was initially presumed. Platt and Pickering conducted a lively debate on this topic. Platt favored the idea that a single gene or only a few genes were responsible for high blood pressure. Pickering presented research results, which supported the assumption that many genes exerted an influence on blood pressure. This was all in a period when it was not even known what genes were. Genome-wide association studies (GWAS) according to the Pickering model have identified > 500 blood pressure relevant gene loci, which are distributed over the whole genome. Each individual gene exerts only a small effect on blood pressure. The dark horses of hypertension research are the secondary causes. In pheochromocytoma, primary aldosteronism, Cushing’s syndrome and even fibromuscular dysplasia (renovascular hypertension) the results indicate that a genetic cause regularly underlies secondary hypertension. This would therefore also partially confirm Platt’s theory. In the meantime, a multitude of forms of hypertension have been described with a genetic inheritance according to Mendel. Each of these genetic variants exerts a considerable influence on blood pressure. A multitude of novel physiological mechanisms were explained by this. These findings will become therapeutically important. Therefore, it is incumbent upon clinicians to be optimally informed about these research results.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5

Literatur

  1. Beaney T, Schutte AE, Tomaszewski M, Ariti C, Burrell LM, Castillo RR, Charchar FJ, Damasceno A, Kruger R, Lackland DT, Nilsson PM, Prabhakaran D, Ramirez AJ, Schlaich MP, Wang J, Weber MA, Poulter NR, Investigators MMM (2018) May Measurement Month 2017: an analysis of blood pressure screening results worldwide. Lancet Glob Health 6:e736–e743

    Article  Google Scholar 

  2. Geldsetzer P, Manne-Goehler J, Marcus ME, Ebert C, Zhumadilov Z, Wesseh CS, Tsabedze L, Supiyev A, Sturua L, Bahendeka SK, Sibai AM, Quesnel-Crooks S, Norov B, Mwangi KJ, Mwalim O, Wong-McClure R, Mayige MT, Martins JS, Lunet N, Labadarios D, Karki KB, Kagaruki GB, Jorgensen JMA, Hwalla NC, Houinato D, Houehanou C, Msaidie M, Guwatudde D, Gurung MS, Gathecha G, Dorobantu M, Damasceno A, Bovet P, Bicaba BW, Aryal KK, Andall-Brereton G, Agoudavi K, Stokes A, Davies JI, Barnighausen T, Atun R, Vollmer S, Jaacks LM (2019) The state of hypertension care in 44 low-income and middle-income countries: a cross-sectional study of nationally representative individual-level data from 1.1 million adults. Lancet 394:652–662

    Article  Google Scholar 

  3. Niiranen TJ, McCabe EL, Larson MG, Henglin M, Lakdawala NK, Vasan RS, Cheng S (2017) Risk for hypertension crosses generations in the community: a multi-generational cohort study. Eur Heart J 38:2300–2308

    Article  Google Scholar 

  4. Grim CE, Miller JZ, Luft FC, Christian JC, Weinberger MH (1979) Genetic influences on renin, aldosterone, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man. Hypertension 1:583–590

    Article  CAS  Google Scholar 

  5. Tarnoki AD, Szalontai L, Fagnani C, Tarnoki DL, Lucatelli P, Maurovich-Horvat P, Jermendy AL, Kovacs A, Molnar AA, Godor E, Fejer B, Hernyes A, Cirelli C, Fanelli F, Farina F, Baracchini C, Meneghetti G, Gyarmathy AV, Jermendy G, Merkely B, Pucci G, Schillaci G, Stazi MA, Medda E (2019) Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima media thickness: a longitudinal twin study. Cardiol J. https://doi.org/10.5603/CJ.a2019.0089

    Article  Google Scholar 

  6. Dominiczak A, Delles C, Padmanabhan S (2017) Genomics and precision medicine for clinicians and scientists in hypertension. Hypertension 69:e10–e13

    CAS  PubMed  Google Scholar 

  7. Hamilton M, Pickering GW, Roberts JA, Sowry GS (1954) The aetiology of essential hypertension. 4. The role of inheritance. Clin Sci 13:273–304

    CAS  PubMed  Google Scholar 

  8. Platt R (1947) Heredity in hypertension. Q J Med 16:111–133

    CAS  PubMed  Google Scholar 

  9. Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W, Kelly TN, Saleheen D, Lehne B, Leach IM, Drong AW, Abbott J, Wahl S, Tan ST, Scott WR, Campanella G, Chadeau-Hyam M, Afzal U, Ahluwalia TS, Bonder MJ, Chen P, Dehghan A, Edwards TL, Esko T, Go MJ, Harris SE, Hartiala J, Kasela S, Kasturiratne A, Khor CC, Kleber ME, Li H, Yu Mok Z, Nakatochi M, Sapari NS, Saxena R, Stewart AFR, Stolk L, Tabara Y, Teh AL, Wu Y, Wu JY, Zhang Y, Aits I, Da Silva Couto Alves A, Das S, Dorajoo R, Hopewell JC, Kim YK, Koivula RW, Luan J, Lyytikainen LP, Nguyen QN, Pereira MA, Postmus I, Raitakari OT, Scannell Bryan M, Scott RA, Sorice R, Tragante V, Traglia M, White J, Yamamoto K, Zhang Y, Adair LS, Ahmed A, Akiyama K, Asif R, Aung T, Barroso I, Bjonnes A, Braun TR, Cai H, Chang LC, Chen CH, Cheng CY, Chong YS, Collins R, Courtney R, Davies G, Delgado G, Do LD, Doevendans PA, Gansevoort RT, Gao YT, Grammer TB, Grarup N, Grewal J, Gu D, Wander GS, Hartikainen AL, Hazen SL, He J, Heng CK, Hixson JE, Hofman A, Hsu C, Huang W, Husemoen LLN, Hwang JY, Ichihara S, Igase M, Isono M, Justesen JM, Katsuya T, Kibriya MG, Kim YJ, Kishimoto M, Koh WP, Kohara K, Kumari M, Kwek K, Lee NR, Lee J, Liao J, Lieb W, Liewald DCM, Matsubara T, Matsushita Y, Meitinger T, Mihailov E, Milani L, Mills R, Mononen N, Muller-Nurasyid M, Nabika T, Nakashima E, Ng HK, Nikus K, Nutile T, Ohkubo T, Ohnaka K, Parish S, Paternoster L, Peng H, Peters A, Pham ST, Pinidiyapathirage MJ, Rahman M, Rakugi H, Rolandsson O, Ann Rozario M, Ruggiero D, Sala CF, Sarju R, Shimokawa K, Snieder H, Sparso T, Spiering W, Starr JM, Stott DJ, Stram DO, Sugiyama T, Szymczak S, Tang WHW, Tong L, Trompet S, Turjanmaa V, Ueshima H, Uitterlinden AG, Umemura S, Vaarasmaki M, van Dam RM, van Gilst WH, van Veldhuisen DJ, Viikari JS, Waldenberger M, Wang Y, Wang A, Wilson R, Wong TY, Xiang YB, Yamaguchi S, Ye X, Young RD, Young TL, Yuan JM, Zhou X, Asselbergs FW, Ciullo M, Clarke R, Deloukas P, Franke A, Franks PW, Franks S, Friedlander Y, Gross MD, Guo Z, Hansen T, Jarvelin MR, Jorgensen T, Jukema JW, Kahonen M, Kajio H, Kivimaki M, Lee JY, Lehtimaki T, Linneberg A, Miki T, Pedersen O, Samani NJ, Sorensen TIA, Takayanagi R, Toniolo D, consortium B, GRAMplusCD CA, LifeLines Cohort S, InterAct C, Ahsan H, Allayee H, Chen YT, Danesh J, Deary IJ, Franco OH, Franke L, Heijman BT, Holbrook JD, Isaacs A, Kim BJ, Lin X, Liu J, Marz W, Metspalu A, Mohlke KL, Sanghera DK, Shu XO, van Meurs JBJ, Vithana E, Wickremasinghe AR, Wijmenga C, Wolffenbuttel BHW, Yokota M, Zheng W, Zhu D, Vineis P, Kyrtopoulos SA, Kleinjans JCS, McCarthy MI, Soong R, Gieger C, Scott J, Teo YY, He J, Elliott P, Tai ES, van der Harst P, Kooner JS and Chambers JC. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nat Genet. 2015;47:1282–1293.

  10. Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson T, Thorleifsson G, Luan J, Donnelly LA, Kanoni S, Petersen AK, Pihur V, Strawbridge RJ, Shungin D, Hughes MF, Meirelles O, Kaakinen M, Bouatia-Naji N, Kristiansson K, Shah S, Kleber ME, Guo X, Lyytikainen LP, Fava C, Eriksson N, Nolte IM, Magnusson PK, Salfati EL, Rallidis LS, Theusch E, Smith AJP, Folkersen L, Witkowska K, Pers TH, Joehanes R, Kim SK, Lataniotis L, Jansen R, Johnson AD, Warren H, Kim YJ, Zhao W, Wu Y, Tayo BO, Bochud M, consortium CH‑E, consortium C‑H, Wellcome Trust Case Control C, Absher D, Adair LS, Amin N, Arking DE, Axelsson T, Baldassarre D, Balkau B, Bandinelli S, Barnes MR, Barroso I, Bevan S, Bis JC, Bjornsdottir G, Boehnke M, Boerwinkle E, Bonnycastle LL, Boomsma DI, Bornstein SR, Brown MJ, Burnier M, Cabrera CP, Chambers JC, Chang IS, Cheng CY, Chines PS, Chung RH, Collins FS, Connell JM, Doring A, Dallongeville J, Danesh J, de Faire U, Delgado G, Dominiczak AF, Doney ASF, Drenos F, Edkins S, Eicher JD, Elosua R, Enroth S, Erdmann J, Eriksson P, Esko T, Evangelou E, Evans A, Fall T, Farrall M, Felix JF, Ferrieres J, Ferrucci L, Fornage M, Forrester T, Franceschini N, Duran OHF, Franco-Cereceda A, Fraser RM, Ganesh SK, Gao H, Gertow K, Gianfagna F, Gigante B, Giulianini F, Goel A, Goodall AH, Goodarzi MO, Gorski M, Grassler J, Groves C, Gudnason V, Gyllensten U, Hallmans G, Hartikainen AL, Hassinen M, Havulinna AS, Hayward C, Hercberg S, Herzig KH, Hicks AA, Hingorani AD, Hirschhorn JN, Hofman A, Holmen J, Holmen OL, Hottenga JJ, Howard P, Hsiung CA, Hunt SC, Ikram MA, Illig T, Iribarren C, Jensen RA, Kahonen M, Kang H, Kathiresan S, Keating BJ, Khaw KT, Kim YK, Kim E, Kivimaki M, Klopp N, Kolovou G, Komulainen P, Kooner JS, Kosova G, Krauss RM, Kuh D, Kutalik Z, Kuusisto J, Kvaloy K, Lakka TA, Lee NR, Lee IT, Lee WJ, Levy D, Li X, Liang KW, Lin H, Lin L, Lindstrom J, Lobbens S, Mannisto S, Muller G, Muller-Nurasyid M, Mach F, Markus HS, Marouli E, McCarthy MI, McKenzie CA, Meneton P, Menni C, Metspalu A, Mijatovic V, Moilanen L, Montasser ME, Morris AD, Morrison AC, Mulas A, Nagaraja R, Narisu N, Nikus K, O’Donnell CJ, O’Reilly PF, Ong KK, Paccaud F, Palmer CD, Parsa A, Pedersen NL, Penninx BW, Perola M, Peters A, Poulter N, Pramstaller PP, Psaty BM, Quertermous T, Rao DC, Rasheed A, Rayner N, Renstrom F, Rettig R, Rice KM, Roberts R, Rose LM, Rossouw J, Samani NJ, Sanna S, Saramies J, Schunkert H, Sebert S, Sheu WH, Shin YA, Sim X, Smit JH, Smith AV, Sosa MX, Spector TD, Stancakova A, Stanton A, Stirrups KE, Stringham HM, Sundstrom J, Swift AJ, Syvanen AC, Tai ES, Tanaka T, Tarasov KV, Teumer A, Thorsteinsdottir U, Tobin MD, Tremoli E, Uitterlinden AG, Uusitupa M, Vaez A, Vaidya D, van Duijn CM, van Iperen EPA, Vasan RS, Verwoert GC, Virtamo J, Vitart V, Voight BF, Vollenweider P, Wagner A, Wain LV, Wareham NJ, Watkins H, Weder AB, Westra HJ, Wilks R, Wilsgaard T, Wilson JF, Wong TY, Yang TP, Yao J, Yengo L, Zhang W, Zhao JH, Zhu X, Bovet P, Cooper RS, Mohlke KL, Saleheen D, Lee JY, Elliott P, Gierman HJ, Willer CJ, Franke L, Hovingh GK, Taylor KD, Dedoussis G, Sever P, Wong A, Lind L, Assimes TL, Njolstad I, Schwarz PE, Langenberg C, Snieder H, Caulfield MJ, Melander O, Laakso M, Saltevo J, Rauramaa R, Tuomilehto J, Ingelsson E, Lehtimaki T, Hveem K, Palmas W, Marz W, Kumari M, Salomaa V, Chen YI, Rotter JI, Froguel P, Jarvelin MR, Lakatta EG, Kuulasmaa K, Franks PW, Hamsten A, Wichmann HE, Palmer CNA, Stefansson K, Ridker PM, Loos RJF, Chakravarti A, Deloukas P, Morris AP, Newton-Cheh C and Munroe PB. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet. 2016;48:1171–1184.

  11. Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, Ntalla I, Surendran P, Liu C, Cook JP, Kraja AT, Drenos F, Loh M, Verweij N, Marten J, Karaman I, Lepe MP, O’Reilly PF, Knight J, Snieder H, Kato N, He J, Tai ES, Said MA, Porteous D, Alver M, Poulter N, Farrall M, Gansevoort RT, Padmanabhan S, Magi R, Stanton A, Connell J, Bakker SJ, Metspalu A, Shields DC, Thom S, Brown M, Sever P, Esko T, Hayward C, van der Harst P, Saleheen D, Chowdhury R, Chambers JC, Chasman DI, Chakravarti A, Newton-Cheh C, Lindgren CM, Levy D, Kooner JS, Keavney B, Tomaszewski M, Samani NJ, Howson JM, Tobin MD, Munroe PB, Ehret GB, Wain LV, International Consortium of Blood Pressure GA, Consortium B, Lifelines Cohort S, Understanding Society Scientific g, Consortium CHDE, Exome BPC, Consortium TDG, Go TDC, Cohorts for H, Ageing Research in Genome Epidemiology BPEC, International Genomics of Blood Pressure C and group UKBCCBw (2017) Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. nat Genet 49:403–415

    Article  CAS  Google Scholar 

  12. Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Ng FL, Evangelou M, Witkowska K, Tzanis E, Hellwege JN, Giri A, Velez Edwards DR, Sun YV, Cho K, Gaziano JM, Wilson PWF, Tsao PS, Kovesdy CP, Esko T, Magi R, Milani L, Almgren P, Boutin T, Debette S, Ding J, Giulianini F, Holliday EG, Jackson AU, Li-Gao R, Lin WY, Luan J, Mangino M, Oldmeadow C, Prins BP, Qian Y, Sargurupremraj M, Shah N, Surendran P, Theriault S, Verweij N, Willems SM, Zhao JH, Amouyel P, Connell J, de Mutsert R, Doney ASF, Farrall M, Menni C, Morris AD, Noordam R, Pare G, Poulter NR, Shields DC, Stanton A, Thom S, Abecasis G, Amin N, Arking DE, Ayers KL, Barbieri CM, Batini C, Bis JC, Blake T, Bochud M, Boehnke M, Boerwinkle E, Boomsma DI, Bottinger EP, Braund PS, Brumat M, Campbell A, Campbell H, Chakravarti A, Chambers JC, Chauhan G, Ciullo M, Cocca M, Collins F, Cordell HJ, Davies G, de Borst MH, de Geus EJ, Deary IJ, Deelen J, Del Greco MF, Demirkale CY, Dorr M, Ehret GB, Elosua R, Enroth S, Erzurumluoglu AM, Ferreira T, Franberg M, Franco OH, Gandin I, Gasparini P, Giedraitis V, Gieger C, Girotto G, Goel A, Gow AJ, Gudnason V, Guo X, Gyllensten U, Hamsten A, Harris TB, Harris SE, Hartman CA, Havulinna AS, Hicks AA, Hofer E, Hofman A, Hottenga JJ, Huffman JE, Hwang SJ, Ingelsson E, James A, Jansen R, Jarvelin MR, Joehanes R, Johansson A, Johnson AD, Joshi PK, Jousilahti P, Jukema JW, Jula A, Kahonen M, Kathiresan S, Keavney BD, Khaw KT, Knekt P, Knight J, Kolcic I, Kooner JS, Koskinen S, Kristiansson K, Kutalik Z, Laan M, Larson M, Launer LJ, Lehne B, Lehtimaki T, Liewald DCM, Lin L, Lind L, Lindgren CM, Liu Y, Loos RJF, Lopez LM, Lu Y, Lyytikainen LP, Mahajan A, Mamasoula C, Marrugat J, Marten J, Milaneschi Y, Morgan A, Morris AP, Morrison AC, Munson PJ, Nalls MA, Nandakumar P, Nelson CP, Niiranen T, Nolte IM, Nutile T, Oldehinkel AJ, Oostra BA, O’Reilly PF, Org E, Padmanabhan S, Palmas W, Palotie A, Pattie A, Penninx B, Perola M, Peters A, Polasek O, Pramstaller PP, Nguyen QT, Raitakari OT, Ren M, Rettig R, Rice K, Ridker PM, Ried JS, Riese H, Ripatti S, Robino A, Rose LM, Rotter JI, Rudan I, Ruggiero D, Saba Y, Sala CF, Salomaa V, Samani NJ, Sarin AP, Schmidt R, Schmidt H, Shrine N, Siscovick D, Smith AV, Snieder H, Sober S, Sorice R, Starr JM, Stott DJ, Strachan DP, Strawbridge RJ, Sundstrom J, Swertz MA, Taylor KD, Teumer A, Tobin MD, Tomaszewski M, Toniolo D, Traglia M, Trompet S, Tuomilehto J, Tzourio C, Uitterlinden AG, Vaez A, van der Most PJ, van Duijn CM, Vergnaud AC, Verwoert GC, Vitart V, Volker U, Vollenweider P, Vuckovic D, Watkins H, Wild SH, Willemsen G, Wilson JF, Wright AF, Yao J, Zemunik T, Zhang W, Attia JR, Butterworth AS, Chasman DI, Conen D, Cucca F, Danesh J, Hayward C, Howson JMM, Laakso M, Lakatta EG, Langenberg C, Melander O, Mook-Kanamori DO, Palmer CNA, Risch L, Scott RA, Scott RJ, Sever P, Spector TD, van der Harst P, Wareham NJ, Zeggini E, Levy D, Munroe PB, Newton-Cheh C, Brown MJ, Metspalu A, Hung AM, O’Donnell CJ, Edwards TL, Psaty BM, Tzoulaki I, Barnes MR, Wain LV, Elliott P, Caulfield MJ, Veteran MP (2018) Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. nat Genet 50:1412–1425

    Article  CAS  Google Scholar 

  13. Giri A, Hellwege JN, Keaton JM, Park J, Qiu C, Warren HR, Torstenson ES, Kovesdy CP, Sun YV, Wilson OD, Robinson-Cohen C, Roumie CL, Chung CP, Birdwell KA, Damrauer SM, DuVall SL, Klarin D, Cho K, Wang Y, Evangelou E, Cabrera CP, Wain LV, Shrestha R, Mautz BS, Akwo EA, Sargurupremraj M, Debette S, Boehnke M, Scott LJ, Luan J, Zhao JH, Willems SM, Theriault S, Shah N, Oldmeadow C, Almgren P, Li-Gao R, Verweij N, Boutin TS, Mangino M, Ntalla I, Feofanova E, Surendran P, Cook JP, Karthikeyan S, Lahrouchi N, Liu C, Sepulveda N, Richardson TG, Kraja A, Amouyel P, Farrall M, Poulter NR, Understanding Society Scientific G, International Consortium for Blood P, Blood Pressure-International Consortium of Exome Chip S, Laakso M, Zeggini E, Sever P, Scott RA, Langenberg C, Wareham NJ, Conen D, Palmer CNA, Attia J, Chasman DI, Ridker PM, Melander O, Mook-Kanamori DO, Harst PV, Cucca F, Schlessinger D, Hayward C, Spector TD, Jarvelin MR, Hennig BJ, Timpson NJ, Wei WQ, Smith JC, Xu Y, Matheny ME, Siew EE, Lindgren C, Herzig KH, Dedoussis G, Denny JC, Psaty BM, Howson JMM, Munroe PB, Newton-Cheh C, Caulfield MJ, Elliott P, Gaziano JM, Concato J, Wilson PWF, Tsao PS, Velez Edwards DR, Susztak K, Million Veteran P, O’Donnell CJ, Hung AM and Edwards TL. Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nat Genet. 2019;51:51–62.

  14. Cabrera CP, Ng FL, Nicholls HL, Gupta A, Barnes MR, Munroe PB, Caulfield MJ (2019) Over 1000 genetic loci influencing blood pressure with multiple systems and tissues implicated. hum Mol Genet 28:R151–R161

    Article  CAS  Google Scholar 

  15. Ng FL, Warren HR, Caulfield MJ (2018) Hypertension genomics and cardiovascular prevention. Ann Transl Med 6:291

    Article  Google Scholar 

  16. Luft FC (2019) Men, mice, and blood pressure: telemetry? kidney Int 96:31–33

    Article  Google Scholar 

  17. Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, Genetic Investigation of ATC (2015) Biological interpretation of genome-wide association studies using predicted gene functions. Nat Commun 6:5890

    Article  CAS  Google Scholar 

  18. Neumann HPH, Young WF Jr., Eng C (2019) Pheochromocytoma and Paraganglioma. n Engl J Med 381:552–565

    Article  CAS  Google Scholar 

  19. Neumann HP, Young WF Jr., Krauss T, Bayley JP, Schiavi F, Opocher G, Boedeker CC, Tirosh A, Castinetti F, Ruf J, Beltsevich D, Walz M, Groeben HT, von Dobschuetz E, Gimm O, Wohllk N, Pfeifer M, Lourenco DM Jr., Peczkowska M, Patocs A, Ngeow J, Makay O, Shah NS, Tischler A, Leijon H, Pennelli G, Villar Gomez de Las Heras K, Links TP, Bausch B, Eng C (2018) 65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma. Endocr Relat Cancer 25:T201–T219

    Article  Google Scholar 

  20. Seidel E, Schewe J, Scholl UI (2019) Genetic causes of primary aldosteronism. Exp Mol Med 51:131

    Article  Google Scholar 

  21. Hannah-Shmouni F, Stratakis CA (2018) An update on the genetics of benign pituitary adenomas in children and adolescents. Curr Opin Endocr Metab Res 1:19–24

    Article  Google Scholar 

  22. Hernandez-Ramirez LC, Stratakis CA (2018) Genetics of Cushing’s syndrome. Endocrinol Metab Clin North Am 47:275–297

    Article  Google Scholar 

  23. Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F, Meitinger T, Mizuno-Yamasaki E, Kawaguchi K, Saeki Y, Tanaka K, Wieland T, Graf E, Saeger W, Ronchi CL, Allolio B, Buchfelder M, Strom TM, Fassnacht M, Komada M (2015) Mutations in the deubiquitinase gene USP8 cause Cushing’s disease. nat Genet 47:31–38

    Article  CAS  Google Scholar 

  24. Kovacic JC (2017) Unraveling the complex genetics of coronary artery disease. j Am Coll Cardiol 69:837–840

    Article  Google Scholar 

  25. Cooper CJ, Murphy TP, Cutlip DE, Jamerson K, Henrich W, Reid DM, Cohen DJ, Matsumoto AH, Steffes M, Jaff MR, Prince MR, Lewis EF, Tuttle KR, Shapiro JI, Rundback JH, Massaro JM, D’Agostino RB Sr., Dworkin LD, Investigators C (2014) Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med 370:13–22

    Article  CAS  Google Scholar 

  26. Di Monaco S, Georges A, Lengele JP, Vikkula M, Persu A (2018) Genomics of fibromuscular dysplasia. Int J Mol Sci 19(5):1526. https://doi.org/10.3390/ijms19051526

    Article  CAS  PubMed Central  Google Scholar 

  27. Kiando SR, Tucker NR, Castro-Vega LJ, Katz A, D’Escamard V, Treard C, Fraher D, Albuisson J, Kadian-Dodov D, Ye Z, Austin E, Yang ML, Hunker K, Barlassina C, Cusi D, Galan P, Empana JP, Jouven X, Gimenez-Roqueplo AP, Bruneval P, Kim HES, Olin JW, Gornik HL, Azizi M, Plouin PF, Ellinor PT, Kullo IJ, Milan DJ, Ganesh SK, Boutouyrie P, Kovacic JC, Jeunemaitre X, Bouatia-Naji N (2016) PHACTR1 is a genetic susceptibility locus for fibromuscular dysplasia supporting its complex genetic pattern of inheritance. Plos Genet 12:e1006367

    Article  Google Scholar 

  28. Luft FC, Schuster H, Bilginturan N, Wienker T (1995) ‘Treasure your exceptions’: what we can learn from autosomal-dominant inherited forms of hypertension. j Hypertens 13:1535–1538

    Article  CAS  Google Scholar 

  29. Levanovich PE et al (2020) Clinical and molecular perspectives of monogenic hypertension. Curr Hypertens Rev. PMID:30963979

  30. Lifton RP, Gharavi AG, Geller DS (2001) Molecular mechanisms of human hypertension. Cell 104:545–556

    Article  CAS  Google Scholar 

  31. Kahle KT, Ring AM, Lifton RP (2008) Molecular physiology of the WNK kinases. Annu Rev Physiol 70:329–355

    Article  CAS  Google Scholar 

  32. Mune T, Rogerson FM, Nikkila H, Agarwal AK, White PC (1995) Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase. nat Genet 10:394–399

    Article  CAS  Google Scholar 

  33. Kurtz TW, DiCarlo SE, Pravenec M, Morris RC Jr. (2018) The pivotal role of renal vasodysfunction in salt sensitivity and the initiation of salt-induced hypertension. Curr Opin Nephrol Hypertens 27:83–92

    Article  CAS  Google Scholar 

  34. Kho J, Tian X, Wong WT, Bertin T, Jiang MM, Chen S, Jin Z, Shchelochkov OA, Burrage LC, Reddy AK, Jiang H, Abo-Zahrah R, Ma S, Zhang P, Bissig KD, Kim JJ, Devaraj S, Rodney GG, Erez A, Bryan NS, Nagamani SCS, Lee BH (2018) Argininosuccinate Lyase deficiency causes an endothelial-dependent form of hypertension. Am J Hum Genet 103:276–287

    Article  CAS  Google Scholar 

  35. Schuster H, Wienker TE, Bahring S, Bilginturan N, Toka HR, Neitzel H, Jeschke E, Toka O, Gilbert D, Lowe A, Ott J, Haller H, Luft FC (1996) Severe autosomal dominant hypertension and brachydactyly in a unique Turkish kindred maps to human chromosome 12. nat Genet 13:98–100

    Article  CAS  Google Scholar 

  36. Maass PG, Aydin A, Luft FC, Schachterle C, Weise A, Stricker S, Lindschau C, Vaegler M, Qadri F, Toka HR, Schulz H, Krawitz PM, Parkhomchuk D, Hecht J, Hollfinger I, Wefeld-Neuenfeld Y, Bartels-Klein E, Muhl A, Kann M, Schuster H, Chitayat D, Bialer MG, Wienker TF, Ott J, Rittscher K, Liehr T, Jordan J, Plessis G, Tank J, Mai K, Naraghi R, Hodge R, Hopp M, Hattenbach LO, Busjahn A, Rauch A, Vandeput F, Gong M, Ruschendorf F, Hubner N, Haller H, Mundlos S, Bilginturan N, Movsesian MA, Klussmann E, Toka O, Bahring S (2015) PDE3A mutations cause autosomal dominant hypertension with brachydactyly. nat Genet 47:647–653

    Article  CAS  Google Scholar 

  37. van den Born BJ, Oskam LC, Zidane M, Schachterle C, Klussmann E, Bahring S, Luft FC (2016) The case a handful of hypertension. kidney Int 90:911–913

    Article  Google Scholar 

  38. Fan P, Zhang D, Yang KQ, Zhang QY, Luo F, Lou Y et al (2019) Hypertension and brachydactyly syndrome associated with vertebral artery malformation caused by a PDE3A missense mutation. Am J Hypertens 33(2):190–197. https://doi.org/10.1093/ajh/hpz151

    Article  CAS  Google Scholar 

  39. Ercu M, Klussmann E (2018) Roles of a‑kinase anchoring proteins and phosphodiesterases in the cardiovascular system. J Cardiovasc Dev Dis. PMID:29461511

  40. Choi YH, Ekholm D, Krall J, Ahmad F, Degerman E, Manganiello VC, Movsesian MA (2001) Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes. biochem J 353:41–50

    Article  CAS  Google Scholar 

  41. Schuster H, Wienker TF, Toka HR, Bahring S, Jeschke E, Toka O, Busjahn A, Hempel A, Tahlhammer C, Oelkers W, Kunze J, Bilginturan N, Haller H, Luft FC (1996) Autosomal dominant hypertension and brachydactyly in a Turkish kindred resembles essential hypertension. Hypertension 28:1085–1092

    Article  CAS  Google Scholar 

  42. Ercu M, Marko L, Schachterle C, Tsvetkov D, Cui Y, Maghsodi S, Bartolomaeus TUP, Maass PG, Zuhlke K, Gregersen N, Hubner N, Hodge R, Muhl A, Pohl B, Illas RM, Geelhaar A, Walter S, Napieczynska H, Schelenz S, Taube M, Heuser A, Anistan YM, Qadri F, Todiras M, Plehm R, Popova E, Langanki R, Eichhorst J, Lehmann M, Wiesner B, Russwurm M, Forslund SK, Kamer I, Muller DN, Gollasch M, Aydin A, Bahring S, Bader M, Luft FC, Klussmann E (2020) Phosphodiesterase 3A and arterial hypertension. Circulation 142:133–149

    Article  CAS  Google Scholar 

  43. Maass PG, Wirth J, Aydin A, Rump A, Stricker S, Tinschert S, Otero M, Tsuchimochi K, Goldring MB, Luft FC, Bahring S (2010) A cis-regulatory site downregulates PTHLH in translocation t(8;12)(q13;p11.2) and leads to Brachydactyly Type E. hum Mol Genet 19:848–860

    Article  CAS  Google Scholar 

  44. Platt R (1947) Heredity in hypertension. Q J Med 16:311

    CAS  PubMed  Google Scholar 

  45. Pickering G (1964) Systemic Arterial Hypertension. In: Fishman AP (Hrsg) Circulation of the Blood. American Physiological Society, Bethesda

    Google Scholar 

  46. Luft FC (2020) Molecular genetics of human hypertension. Curr Opin Cardiol 35(3):249–257. https://doi.org/10.1097/HCO.0000000000000722

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, Lindenbergerweg 80, 13125, Berlin, Deutschland

    F. C. Luft

Authors
  1. F. C. Luft
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. C. Luft.

Ethics declarations

Interessenkonflikt

F. C. Luft gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Redaktion

H. Haller, Hannover

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luft, F.C. Molekulargenetik der humanen Hypertonie. Internist 62, 223–235 (2021). https://doi.org/10.1007/s00108-021-00979-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00108-021-00979-1

Schlüsselwörter

Keywords

Search

Navigation