The Association of the Vanin-1 N131S Variant with Blood Pressure Is Mediated by Endoplasmic Reticulum-Associated Degradation and Loss of Function

English version České info

Hypertension (HTN) or high blood pressure (BP) is common worldwide and a major risk factor for cardiovascular disease and all-cause mortality. Identification of genetic variants of consequence for HTN serves as the molecular basis for its treatment. Using admixture mapping analysis of the Family Blood Pressure Program data, we recently identified that the VNN1 gene (encoding the protein vanin-1), in particular SNP rs2272996 (N131S), was associated with BP in both African Americans and Mexican Americans. Vanin-1 was reported to act as an oxidative stress sensor using its pantetheinase enzyme activity. Because a linkage between oxidative stress and HTN has been hypothesized for many years, vanin-1's pantetheinase activity offers a physiologic rationale for BP regulation. Here, we first replicated the association of rs2272996 with BP in the Continental Origins and Genetic Epidemiology Network (COGENT), which included nearly 30,000 African Americans. We further demonstrated that the N131S mutation in vanin-1 leads to its rapid degradation in cells, resulting in loss of function on the plasma membrane. The loss of function of vanin-1 is associated with reduced BP. Therefore, our results indicate that vanin-1 is a new candidate to be manipulated to ameliorate HTN.

Vyšlo v časopise: The Association of the Vanin-1 N131S Variant with Blood Pressure Is Mediated by Endoplasmic Reticulum-Associated Degradation and Loss of Function. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004641
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004641

Souhrn

Zdroje

1. LewingtonS, ClarkeR, QizilbashN, PetoR, CollinsR (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360: 1903–1913.

2. CutlerJA, SorliePD, WolzM, ThomT, FieldsLE, et al. (2008) Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988–1994 and 1999–2004. Hypertension 52: 818–827.

3. LevyD, DeStefanoAL, LarsonMG, O'DonnellCJ, LiftonRP, et al. (2000) Evidence for a gene influencing blood pressure on chromosome 17. Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the framingham heart study. Hypertension 36: 477–483.

4. RogerVL, GoAS, Lloyd-JonesDM, BenjaminEJ, BerryJD, et al. (2012) Executive summary: heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation 125: 188–197.

5. HertzRP, UngerAN, CornellJA, SaundersE (2005) Racial disparities in hypertension prevalence, awareness, and management. Arch Intern Med 165: 2098–2104.

6. StevensJ, TruesdaleKP, KatzEG, CaiJ (2008) Impact of body mass index on incident hypertension and diabetes in Chinese Asians, American Whites, and American Blacks: the People's Republic of China Study and the Atherosclerosis Risk in Communities Study. Am J Epidemiol 167: 1365–1374.

7. SelassieA, WagnerCS, LakenML, FergusonML, FerdinandKC, et al. (2011) Progression is accelerated from prehypertension to hypertension in blacks. Hypertension 58: 579–587.

8. ChobanianAV, BakrisGL, BlackHR, CushmanWC, GreenLA, et al. (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42: 1206–1252.

9. BerryJD, DyerA, CaiX, GarsideDB, NingH, et al. (2012) Lifetime risks of cardiovascular disease. N Engl J Med 366: 321–329.

10. SamaniNJ (2003) Genome scans for hypertension and blood pressure regulation. Am J Hypertens 16: 167–171.

11. ZhuX, LukeA, CooperRS, QuertermousT, HanisC, et al. (2005) Admixture mapping for hypertension loci with genome-scan markers. Nat Genet 37: 177–181.

12. ZhuX, CooperRS (2007) Admixture mapping provides evidence of association of the VNN1 gene with hypertension. PLoS One 2: e1244.

13. FavaC, MontagnanaM, DaneseE, SjogrenM, AlmgrenP, et al. (2013) Vanin-1 T26I polymorphism, hypertension and cardiovascular events in two large urban-based prospective studies in Swedes. Nutr Metab Cardiovasc Dis 23: 53–60.

14. Aurrand-LionsM, GallandF, BazinH, ZakharyevVM, ImhofBA, et al. (1996) Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing. Immunity 5: 391–405.

15. MayorS, RiezmanH (2004) Sorting GPI-anchored proteins. Nat Rev Mol Cell Biol 5: 110–120.

16. JansenPA, KamsteegM, Rodijk-OlthuisD, van Vlijmen-WillemsIM, de JonghGJ, et al. (2009) Expression of the vanin gene family in normal and inflamed human skin: induction by proinflammatory cytokines. J Invest Dermatol 129: 2167–2174.

17. MarasB, BarraD, DupreS, PitariG (1999) Is pantetheinase the actual identity of mouse and human vanin-1 proteins? FEBS Lett 461: 149–152.

18. PitariG, MalergueF, MartinF, PhilippeJM, MassucciMT, et al. (2000) Pantetheinase activity of membrane-bound Vanin-1: lack of free cysteamine in tissues of Vanin-1 deficient mice. FEBS Lett 483: 149–154.

19. BrionesAM, TouyzRM (2010) Oxidative stress and hypertension: current concepts. Curr Hypertens Rep 12: 135–142.

20. HarrisonDG, GongoraMC (2009) Oxidative stress and hypertension. Med Clin North Am 93: 621–635.

21. NambiarS, ViswanathanS, ZachariahB, HanumanthappaN, MagadiSG (2009) Oxidative stress in prehypertension: rationale for antioxidant clinical trials. Angiology 60: 221–234.

22. KaskowBJ, DiepeveenLA, Michael ProffittJ, ReaAJ, UlgiatiD, et al. (2014) Molecular prioritization strategies to identify functional genetic variants in the cardiovascular disease-associated expression QTL Vanin-1. Eur J Hum Genet 22: 688–695.

23. KaskowBJ, ProffittJM, BlangeroJ, MosesEK, AbrahamLJ (2012) Diverse biological activities of the vascular non-inflammatory molecules - the Vanin pantetheinases. Biochem Biophys Res Commun 417: 653–658.

24. ZhangB, LoC, ShenL, SoodR, JonesC, et al. (2011) The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP. Blood 117: 4569–4579.

25. ChenS, ZhangW, TangC, TangX, LiuL, et al. (2014) Vanin-1 is a key activator for hepatic gluconeogenesis. Diabetes 63: 2073–2085.

26. BerruyerC, MartinFM, CastellanoR, MaconeA, MalergueF, et al. (2004) Vanin-1−/− mice exhibit a glutathione-mediated tissue resistance to oxidative stress. Mol Cell Biol 24: 7214–7224.

27. MartinF, PenetMF, MalergueF, LepidiH, DesseinA, et al. (2004) Vanin-1(−/−) mice show decreased NSAID- and Schistosoma-induced intestinal inflammation associated with higher glutathione stores. J Clin Invest 113: 591–597.

28. PouyetL, Roisin-BouffayC, ClementA, MilletV, GarciaS, et al. (2010) Epithelial vanin-1 controls inflammation-driven carcinogenesis in the colitis-associated colon cancer model. Inflamm Bowel Dis 16: 96–104.

29. FranceschiniN, FoxE, ZhangZ, EdwardsTL, NallsMA, et al. (2013) Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations. Am J Hum Genet 93: 545–554.

30. TobinMD, SheehanNA, ScurrahKJ, BurtonPR (2005) Adjusting for treatment effects in studies of quantitative traits: antihypertensive therapy and systolic blood pressure. Stat Med 24: 2911–2935.

31. MantelN, HaenszelW (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719–748.

32. WillerCJ, LiY, AbecasisGR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26: 2190–2191.

33. DerSimonianR, LairdN (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.

34. DammanahalliKJ, StevensS, TerkeltaubR (2012) Vanin-1 pantetheinase drives smooth muscle cell activation in post-arterial injury neointimal hyperplasia. PLoS One 7: e39106.

35. DiXJ, HanDY, WangYJ, ChanceMR, MuTW (2013) SAHA enhances Proteostasis of epilepsy-associated alpha1(A322D)beta2gamma2 GABA(A) receptors. Chem Biol 20: 1456–1468.

36. RuanBH, ColeDC, WuP, QuaziA, PageK, et al. (2010) A fluorescent assay suitable for inhibitor screening and vanin tissue quantification. Anal Biochem 399: 284–292.

37. TriggleDJ (2006) L-type calcium channels. Curr Pharm Des 12: 443–457.

38. TomiyamaH, YamashinaA (2014) Beta-Blockers in the Management of Hypertension and/or Chronic Kidney Disease. Int J Hypertens 2014: 919256.

39. EhretGB, MunroePB, RiceKM, BochudM, JohnsonAD, et al. (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478: 103–109.

40. KatoN, TakeuchiF, TabaraY, KellyTN, GoMJ, et al. (2011) Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet 43: 531–538.

41. ZhuX, YoungJH, FoxE, KeatingBJ, FranceschiniN, et al. (2011) Combined admixture mapping and association analysis identifies a novel blood pressure genetic locus on 5p13: contributions from the CARe consortium. Hum Mol Genet 20: 2285–2295.

42. JordanCT, CaoL, RobersonED, DuanS, HelmsCA, et al. (2012) Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. Am J Hum Genet 90: 796–808.

43. TeslovichTM, MusunuruK, SmithAV, EdmondsonAC, StylianouIM, et al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466: 707–713.

44. FrazerKA, BallingerDG, CoxDR, HindsDA, StuveLL, et al. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851–861.

45. AbecasisGR, AltshulerD, AutonA, BrooksLD, DurbinRM, et al. (2010) A map of human genome variation from population-scale sequencing. Nature 467: 1061–1073.

46. DunhamI, KundajeA, AldredSF, CollinsPJ, DavisCA, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74.

47. BrennerC (2002) Catalysis in the nitrilase superfamily. Curr Opin Struct Biol 12: 775–782.

48. RoyA, KucukuralA, ZhangY (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5: 725–738.

49. HebertDN, MolinariM (2012) Flagging and docking: dual roles for N-glycans in protein quality control and cellular proteostasis. Trends Biochem Sci 37: 404–410.

50. HeleniusA, TrombettaES, HebertDN, SimonsJF (1997) Calnexin, calreticulin and the folding of glycoproteins. Trends in Cell Biology 7: 193–200.

51. OngDS, WangYJ, TanYL, YatesJR3rd, MuTW, et al. (2013) FKBP10 depletion enhances glucocerebrosidase proteostasis in Gaucher disease fibroblasts. Chem Biol 20: 403–415.

52. ChristiansonJC, OlzmannJA, ShalerTA, SowaME, BennettEJ, et al. (2012) Defining human ERAD networks through an integrative mapping strategy. Nat Cell Biol 14: 93–105.

53. VembarSS, BrodskyJL (2008) One step at a time: endoplasmic reticulum-associated degradation. Nat Rev Mol Cell Biol 9: 944–957.

54. MuTW, OngDS, WangYJ, BalchWE, YatesJR3rd, et al. (2008) Chemical and biological approaches synergize to ameliorate protein-folding diseases. Cell 134: 769–781.

55. WangYJ, DiXJ, MuTW (2014) Using pharmacological chaperones to restore proteostasis. Pharmacol Res 83: 3–9.

56. BalchWE, MorimotoRI, DillinA, KellyJW (2008) Adapting proteostasis for disease intervention. Science 319: 916–919.

57. KimYE, HippMS, BracherA, Hayer-HartlM, HartlFU (2013) Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem 82: 323–355.

58. TayoBO, TeilM, TongL, QinH, KhitrovG, et al. (2011) Genetic background of patients from a university medical center in Manhattan: implications for personalized medicine. PLoS One 6: e19166.

59. FoxER, YoungJH, LiY, DreisbachAW, KeatingBJ, et al. (2011) Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study. Hum Mol Genet 20: 2273–2284.

60. ZhuY, HollmenJ, RatyR, AaltoY, NagyB, et al. (2002) Investigatory and analytical approaches to differential gene expression profiling in mantle cell lymphoma. Br J Haematol 119: 905–915.

61. PriceAL, PattersonNJ, PlengeRM, WeinblattME, ShadickNA, et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38: 904–909.

62. ChenMH, YangQ (2010) GWAF: an R package for genome-wide association analyses with family data. Bioinformatics 26: 580–581.

63. WangYJ, HanDY, TabibT, YatesJR3rd, MuTW (2013) Identification of GABA(C) receptor protein homeostasis network components from three tandem mass spectrometry proteomics approaches. J Proteome Res 12: 5570–5586.