biostudies-literatureWang YJNHLBI NIH HHSNIMHD NIH HHSNHGRI NIH HHSe1004641https://www.ebi.ac.uk/biostudies/studies/S-EPMC4169380biostudies-literatureUnknown10(9)High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single nucleotide polymorphism)-rs2272996-in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P=0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 protein levels. We observed that the N131S vanin-1 is subjected to raPLoS geneticsThe association of the vanin-1 N131S variant with blood pressure is mediated by endoplasmic reticulum-associated degradation and loss of function.PMC4169380P20 MD006899R01 HG003054HL086718T32 HL007567HL007567-29HG003054R01 HL053353R01 HL086718HL053353Psaty BMGottesman OCooper RSGuo XRice KMorrison ACChasman DIMoore JHMosley THWilliams SMFox ESung YJRotimi CNKeating BJMargolis KRisch NWeir DRMusani SKPalmas WEdwards TLWang YJRedline SHoward VJChen WMAdeyemo ALevy DLoos RFeng TYoung JEdwards DRNalls MAYanek LRBecker LCSchork NJArnett DCOGENT BP consortiumKardia SLVasan RZhao WLotay VTang HEaton CCarty CPapanicolaou GSmith JAMurray SSGarcia MERidker PMTaylor KDReiner APHeiss GMartin LWBecker DMFaul JDDreisbach AWHunt SCZhu XWiggins KSalako BKeene KLOgunniyi ARotter JIJohnson ADAndrews JSShriner DGao JBoerwinkle EWang HZonderman ABRao DChen WKeller MFChen GHirschhron JNFranceschini NMu TWChen FBroeckel UBerenson GEvans MKLi YSale MMElston RCPenman AFornage MLiu KTayo BOLettre GDing JBandyopadhyay ALiu YLanktree MBSun YVSrinivasan SJensen RPolak JFChakravarti ASingleton ABCushman MNyberg FHarris TDuan QGuangfa ZBottinger EZhang ZfalseThe association of the vanin-1 N131S variant with blood pressure is mediated by endoplasmic reticulum-associated degradation and loss of function.High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single nucleotide polymorphism)-rs2272996-in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P=0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 protein levels. We observed that the N131S vanin-1 is subjected to ra2014-01-01T00:00:00Z2014 Sep2026-04-30T18:17:37.7Z2019-03-27T01:36:01ZS-EPMC41693802523345410.1371/journal.pgen.1004641