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  • Reid, SarahUppsala universitet,Uppsala University,Uppsala Univ, Sweden,Reumatologi,Science for Life Laboratory, SciLifeLab (författare)

Interaction between the STAT4 rs11889341(T) risk allele and smoking confers increased risk of myocardial infarction and nephritis in patients with systemic lupus erythematosus

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-03-25
  • BMJ,2021
  • 7 s.

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:3a9c75cb-710b-4991-8da2-c893b51beeab
  • https://lup.lub.lu.se/record/3a9c75cb-710b-4991-8da2-c893b51beeabURI
  • https://doi.org/10.1136/annrheumdis-2020-219727DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-178731URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-453080URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:147457082URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Funding Agencies|Swedish Research Council for Medicine and Health [D0283001]; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Ake Wibergs foundation; Gustafssons foundation; Selanders foundation; Norsk Revmatikerforbunds Forskningsfond; Pahles legat og Stortuens legat; Swedish Society for Medical Research [S20-0127]
  • Title in WoS: Interaction between the STAT4 rs11889341(T) risk allele and smoking confers increased risk of myocardial infarction and nephritis in patients with systemic lupus erythematosus
  • Objective: To investigate how genetics influence the risk of smoking-related systemic lupus erythematosus (SLE) manifestations. Methods: Patients with SLE (ndiscovery cohort=776, nreplication cohort=836) were genotyped using the 200K Immunochip single nucleotide polymorphisms (SNP) Array (Illumina) and a custom array. Sixty SNPs with SLE association (p<5.0×10-8) were analysed. Signal transducer and activator of transcription 4 (STAT4) activation was assessed in in vitro stimulated peripheral blood mononuclear cells from healthy controls (n=45). Results: In the discovery cohort, smoking was associated with myocardial infarction (MI) (OR 1.96 (95% CI 1.09 to 3.55)), with a greater effect in patients carrying any rs11889341 STAT4 risk allele (OR 2.72 (95% CI 1.24 to 6.00)) or two risk alleles (OR 8.27 (95% CI 1.48 to 46.27)). Smokers carrying the risk allele also displayed an increased risk of nephritis (OR 1.47 (95% CI 1.06 to 2.03)). In the replication cohort, the high risk of MI in smokers carrying the risk allele and the association between the STAT4 risk allele and nephritis in smokers were confirmed (OR 6.19 (95% CI 1.29 to 29.79) and 1.84 (95% CI 1.05 to 3.29), respectively). The interaction between smoking and the STAT4 risk allele resulted in further increase in the risk of MI (OR 2.14 (95% CI 1.01 to 4.62)) and nephritis (OR 1.53 (95% CI 1.08 to 2.17)), with 54% (MI) and 34% (nephritis) of the risk attributable to the interaction. Levels of interleukin-12-induced phosphorylation of STAT4 in CD8+ T cells were higher in smokers than in non-smokers (mean geometric fluorescence intensity 1063 vs 565, p=0.0063). Lastly, the IL12A rs564799 risk allele displayed association with MI in both cohorts (OR 1.53 (95% CI 1.01 to 2.31) and 2.15 (95% CI 1.08 to 4.26), respectively). Conclusions: Smoking in the presence of the STAT4 risk gene variant appears to increase the risk of MI and nephritis in SLE. Our results also highlight the role of the IL12-STAT4 pathway in SLE-cardiovascular morbidity.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Hagberg, Niklas,1977-Uppsala universitet,Uppsala University,Uppsala Univ, Sweden,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)nihag031 (författare)
  • Sandling, Johanna K.Uppsala universitet,Uppsala University,Uppsala Univ, Sweden,Science for Life Laboratory, SciLifeLab,Reumatologi(Swepub:uu)josan062 (författare)
  • Alexsson, AndreiUppsala universitet,Uppsala University,Uppsala Univ, Sweden,Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden.,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)andax639 (författare)
  • Pucholt, Pascal,Dr,1985-Uppsala universitet,Uppsala University,Uppsala Univ, Sweden,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)paspu920 (författare)
  • Sjöwall, ChristopherLinköpings universitet,Linköping University,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland,Linköping Univ, Div Inflammat & Infect, Dept Biomed & Clin Sci, Linköping, Sweden.(Swepub:liu)chrsj93 (författare)
  • Lerang, KarolineOslo university hospital,Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway. (författare)
  • Jönsen, AndreasLund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital,Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden.(Swepub:lu)reum-ajo (författare)
  • Gunnarsson, IvaKarolinska Institutet,Karolinska Institute,Karolinska University Hospital,Karolinska Inst, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (författare)
  • Syvänen, Ann-Christine,1950-Uppsala universitet,Uppsala University,Uppsala Univ, Sweden,Science for Life Laboratory, SciLifeLab,Reumatologi(Swepub:uu)anncsyva (författare)
  • Troldborg, Anne MargretheAarhus University,Aarhus University Hospital,Aarhus Univ Hosp, Dept Rheumatol, Aarhus, Denmark.;Aarhus Univ, Dept Biomed, Aarhus, Denmark. (författare)
  • Voss, AnneOdense University Hospital,Odense Univ Hosp, Dept Rheumatol, Odense, Denmark. (författare)
  • Bengtsson, Anders A.Lund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)reum-abe (författare)
  • Molberg, ØyvindOslo university hospital,Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway. (författare)
  • Jacobsen, SørenUniversity of Copenhagen,Copenhagen University Hospital,Rigshosp, Copenhagen Univ Hosp, Ctr Rheumatol & Spine Dis, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark. (författare)
  • Svenungsson, ElisabetKarolinska Institutet,Karolinska Institute,Karolinska University Hospital,Karolinska Inst, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (författare)
  • Rönnblom, LarsUppsala universitet,Uppsala University,Uppsala Univ, Sweden,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)larsronn (författare)
  • Leonard, Dag,1975-Uppsala universitet,Uppsala University,Uppsala Univ, Sweden,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)dagle338 (författare)
  • Molberg, O (författare)
  • Uppsala UniversityUppsala Univ, Sweden (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Annals of the Rheumatic Diseases: BMJ80:9, s. 1183-11890003-49671468-2060

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