Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease

Vibeke Andersen, Jane Christensen, Anja Ernst, Bent Ascanius Jacobsen, Anne Tjønneland, Henrik Bygum Krarup, Ulla Vogel

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD).

    METHODS: Genotypes of nuclear factor (NF)-κB (NFKB1) NFκB -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-γ (PPARγ) PPARγ Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn’s disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models.

    RESULTS: The PXR A7635G variant, the PPARγ Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively).

    CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.
    OriginalsprogEngelsk
    TidsskriftWorld Journal of Gastroenterology
    Vol/bind17
    Udgave nummer2
    Sider (fra-til)197-206
    ISSN1007-9327
    DOI
    StatusUdgivet - 2011

    Emneord

      Citer dette

      Andersen, V., Christensen, J., Ernst, A., Jacobsen, B. A., Tjønneland, A., Krarup, H. B., & Vogel, U. (2011). Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease. World Journal of Gastroenterology, 17(2), 197-206. https://doi.org/doi:10.3748/wjg.v17.i2.197
      Andersen, Vibeke ; Christensen, Jane ; Ernst, Anja ; Jacobsen, Bent Ascanius ; Tjønneland, Anne ; Krarup, Henrik Bygum ; Vogel, Ulla. / Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease. I: World Journal of Gastroenterology. 2011 ; Bind 17, Nr. 2. s. 197-206.
      @article{73439b74fa9f48a689491718d74517e4,
      title = "Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease",
      abstract = "AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-κB (NFKB1) NFκB -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-γ (PPARγ) PPARγ Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn’s disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95{\%} CI were estimated by logistic regression models. RESULTS: The PXR A7635G variant, the PPARγ Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95{\%} CI: 1.03-1.66, P = 0.03, OR: 2.30, 95{\%} CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95{\%} CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95{\%} CI: 1.05-1.91, P = 0.02, OR: 1.63, 95{\%} CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95{\%} CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95{\%} CI: 1.03-1.75 and OR: 2.49, 95{\%} CI: 1.24-5.03, respectively). CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.",
      keywords = "Crohn’s disease, Genetic susceptibility, Single nucleotide polymorphisms, Smoking status, Transcription factors, Ulcerative colitis",
      author = "Vibeke Andersen and Jane Christensen and Anja Ernst and Jacobsen, {Bent Ascanius} and Anne Tj{\o}nneland and Krarup, {Henrik Bygum} and Ulla Vogel",
      year = "2011",
      doi = "doi:10.3748/wjg.v17.i2.197",
      language = "English",
      volume = "17",
      pages = "197--206",
      journal = "World Journal of Gastroenterology",
      issn = "1007-9327",
      publisher = "Baishideng Publishing Group Co., Limited",
      number = "2",

      }

      Andersen, V, Christensen, J, Ernst, A, Jacobsen, BA, Tjønneland, A, Krarup, HB & Vogel, U 2011, 'Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease' World Journal of Gastroenterology, bind 17, nr. 2, s. 197-206. https://doi.org/doi:10.3748/wjg.v17.i2.197

      Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease. / Andersen, Vibeke ; Christensen, Jane; Ernst, Anja; Jacobsen, Bent Ascanius; Tjønneland, Anne ; Krarup, Henrik Bygum; Vogel, Ulla.

      I: World Journal of Gastroenterology, Bind 17, Nr. 2, 2011, s. 197-206.

      Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

      TY - JOUR

      T1 - Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease

      AU - Andersen, Vibeke

      AU - Christensen, Jane

      AU - Ernst, Anja

      AU - Jacobsen, Bent Ascanius

      AU - Tjønneland, Anne

      AU - Krarup, Henrik Bygum

      AU - Vogel, Ulla

      PY - 2011

      Y1 - 2011

      N2 - AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-κB (NFKB1) NFκB -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-γ (PPARγ) PPARγ Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn’s disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models. RESULTS: The PXR A7635G variant, the PPARγ Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively). CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.

      AB - AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-κB (NFKB1) NFκB -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-γ (PPARγ) PPARγ Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn’s disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models. RESULTS: The PXR A7635G variant, the PPARγ Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively). CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.

      KW - Crohn’s disease

      KW - Genetic susceptibility

      KW - Single nucleotide polymorphisms

      KW - Smoking status

      KW - Transcription factors

      KW - Ulcerative colitis

      U2 - doi:10.3748/wjg.v17.i2.197

      DO - doi:10.3748/wjg.v17.i2.197

      M3 - Journal article

      VL - 17

      SP - 197

      EP - 206

      JO - World Journal of Gastroenterology

      JF - World Journal of Gastroenterology

      SN - 1007-9327

      IS - 2

      ER -

      Andersen V, Christensen J, Ernst A, Jacobsen BA, Tjønneland A, Krarup HB et al. Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease. World Journal of Gastroenterology. 2011;17(2):197-206. https://doi.org/doi:10.3748/wjg.v17.i2.197