Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetesCitation formats

  • External authors:
  • M. Quaranta
  • A. D. Burden
  • J. N. Barker
  • R. C. Trembath
  • F. Capon

Standard

Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes. / Quaranta, M.; Burden, A. D.; Griffiths, C. E M; Worthington, J.; Barker, J. N.; Trembath, R. C.; Capon, F.

In: Genes and Immunity, Vol. 10, No. 7, 2009, p. 654-658.

Research output: Contribution to journalArticlepeer-review

Harvard

Quaranta, M, Burden, AD, Griffiths, CEM, Worthington, J, Barker, JN, Trembath, RC & Capon, F 2009, 'Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes', Genes and Immunity, vol. 10, no. 7, pp. 654-658. https://doi.org/10.1038/gene.2009.51

APA

Quaranta, M., Burden, A. D., Griffiths, C. E. M., Worthington, J., Barker, J. N., Trembath, R. C., & Capon, F. (2009). Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes. Genes and Immunity, 10(7), 654-658. https://doi.org/10.1038/gene.2009.51

Vancouver

Author

Quaranta, M. ; Burden, A. D. ; Griffiths, C. E M ; Worthington, J. ; Barker, J. N. ; Trembath, R. C. ; Capon, F. / Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes. In: Genes and Immunity. 2009 ; Vol. 10, No. 7. pp. 654-658.

Bibtex

@article{6d43d6bae6334f6583029a1fca103d57,
title = "Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes",
abstract = "Psoriasis is an immune-mediated skin disorder, which is inherited as a complex trait. Genome-wide linkage and association studies have identified a major disease susceptibility locus on chromosome 6p21, as well as a number of genetic determinants of smaller effect. Our group has also documented a significant association between psoriasis and CDKAL1, a gene previously implicated in the pathogenesis of Crohn's disease (CD) and type II diabetes (TIID). With this study, we validate this association, through the analysis of CDKAL1 single nucleotide polymorphism (SNP) rs6908425 in an independently ascertained psoriasis dataset (replication sample: 1323 cases vs 1368 controls, P = 0.00012, odds ratio (OR): 1.28; combined sample: 2579 cases vs 4306 controls, P = 4 × 10-6, OR: 1.26). We also show that the association with psoriasis and CD is completely independent from that with TIID. Finally, we report the results of expression studies demonstrating that CDKAL1 transcripts are virtually absent from skin keratinocytes, but are abundantly expressed in immune cells, especially in CD4+ and CD19+ lymphocytes. It is to be noted that our data indicate that CDKAL1 becomes markedly downregulated when immune cells are activated with proliferating signals. Taken together, our results document the presence of allelic heterogeneity at the CDKAL1 locus and suggest that CDKAL1 alleles may confer susceptibility to clinically distinct disorders through differential effects on disease-specific cell types.",
author = "M. Quaranta and Burden, {A. D.} and Griffiths, {C. E M} and J. Worthington and Barker, {J. N.} and Trembath, {R. C.} and F. Capon",
note = "068545/Z/02, Wellcome Trust, United KingdomG0000934, Medical Research Council, United Kingdom",
year = "2009",
doi = "10.1038/gene.2009.51",
language = "English",
volume = "10",
pages = "654--658",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Springer Nature",
number = "7",

}

RIS

TY - JOUR

T1 - Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes

AU - Quaranta, M.

AU - Burden, A. D.

AU - Griffiths, C. E M

AU - Worthington, J.

AU - Barker, J. N.

AU - Trembath, R. C.

AU - Capon, F.

N1 - 068545/Z/02, Wellcome Trust, United KingdomG0000934, Medical Research Council, United Kingdom

PY - 2009

Y1 - 2009

N2 - Psoriasis is an immune-mediated skin disorder, which is inherited as a complex trait. Genome-wide linkage and association studies have identified a major disease susceptibility locus on chromosome 6p21, as well as a number of genetic determinants of smaller effect. Our group has also documented a significant association between psoriasis and CDKAL1, a gene previously implicated in the pathogenesis of Crohn's disease (CD) and type II diabetes (TIID). With this study, we validate this association, through the analysis of CDKAL1 single nucleotide polymorphism (SNP) rs6908425 in an independently ascertained psoriasis dataset (replication sample: 1323 cases vs 1368 controls, P = 0.00012, odds ratio (OR): 1.28; combined sample: 2579 cases vs 4306 controls, P = 4 × 10-6, OR: 1.26). We also show that the association with psoriasis and CD is completely independent from that with TIID. Finally, we report the results of expression studies demonstrating that CDKAL1 transcripts are virtually absent from skin keratinocytes, but are abundantly expressed in immune cells, especially in CD4+ and CD19+ lymphocytes. It is to be noted that our data indicate that CDKAL1 becomes markedly downregulated when immune cells are activated with proliferating signals. Taken together, our results document the presence of allelic heterogeneity at the CDKAL1 locus and suggest that CDKAL1 alleles may confer susceptibility to clinically distinct disorders through differential effects on disease-specific cell types.

AB - Psoriasis is an immune-mediated skin disorder, which is inherited as a complex trait. Genome-wide linkage and association studies have identified a major disease susceptibility locus on chromosome 6p21, as well as a number of genetic determinants of smaller effect. Our group has also documented a significant association between psoriasis and CDKAL1, a gene previously implicated in the pathogenesis of Crohn's disease (CD) and type II diabetes (TIID). With this study, we validate this association, through the analysis of CDKAL1 single nucleotide polymorphism (SNP) rs6908425 in an independently ascertained psoriasis dataset (replication sample: 1323 cases vs 1368 controls, P = 0.00012, odds ratio (OR): 1.28; combined sample: 2579 cases vs 4306 controls, P = 4 × 10-6, OR: 1.26). We also show that the association with psoriasis and CD is completely independent from that with TIID. Finally, we report the results of expression studies demonstrating that CDKAL1 transcripts are virtually absent from skin keratinocytes, but are abundantly expressed in immune cells, especially in CD4+ and CD19+ lymphocytes. It is to be noted that our data indicate that CDKAL1 becomes markedly downregulated when immune cells are activated with proliferating signals. Taken together, our results document the presence of allelic heterogeneity at the CDKAL1 locus and suggest that CDKAL1 alleles may confer susceptibility to clinically distinct disorders through differential effects on disease-specific cell types.

U2 - 10.1038/gene.2009.51

DO - 10.1038/gene.2009.51

M3 - Article

C2 - 19587699

VL - 10

SP - 654

EP - 658

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 7

ER -