Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis

Nikolai Dyrberg Loft; Lone Skov; Mads Kirchheiner Rasmussen; Robert Gniadecki; Tomas Norman Dam; Ivan Brandslund; Hans Jürgen Hoffmann; Malene Rohr Andersen; Ram Benny Dessau; Ann Christina Bergmann; Niels Møller Andersen; Mikkel Kramme Abildtoft; Paal Skytt Andersen; Merete Lund Hetland; Bente Glintborg; Steffen Bank; Ulla Vogel; Vibeke Andersen

doi:10.1371/journal.pone.0192010

Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis

Nikolai Dyrberg Loft^*, Lone Skov, Mads Kirchheiner Rasmussen, Robert Gniadecki, Tomas Norman Dam, Ivan Brandslund, Hans Jürgen Hoffmann, Malene Rohr Andersen, Ram Benny Dessau, Ann Christina Bergmann, Niels Møller Andersen, Mikkel Kramme Abildtoft, Paal Skytt Andersen, Merete Lund Hetland, Bente Glintborg, Steffen Bank, Ulla Vogel, Vibeke Andersen

^*Corresponding author for this work

Department of Clinical Medicine

19 Citations (Scopus)

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Abstract

Background Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables. Methods Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO. Results Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO. Conclusion Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.

Original language	English
Article number	e0192010
Journal	PLoS ONE
Volume	13
Issue number	2
Number of pages	12
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0192010
Publication status	Published - 2018

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Loft, N. D., Skov, L., Rasmussen, M. K., Gniadecki, R., Dam, T. N., Brandslund, I., Hoffmann, H. J., Andersen, M. R., Dessau, R. B., Bergmann, A. C., Møller Andersen, N., Abildtoft, M. K., Andersen, P. S., Hetland, M. L., Glintborg, B., Bank, S., Vogel, U., & Andersen, V. (2018). Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis. PLoS ONE, 13(2), [e0192010]. https://doi.org/10.1371/journal.pone.0192010

Loft, ND, Skov, L, Rasmussen, MK, Gniadecki, R, Dam, TN, Brandslund, I, Hoffmann, HJ, Andersen, MR, Dessau, RB, Bergmann, AC, Møller Andersen, N, Abildtoft, MK, Andersen, PS, Hetland, ML, Glintborg, B, Bank, S, Vogel, U & Andersen, V 2018, 'Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis', PLoS ONE, vol. 13, no. 2, e0192010. https://doi.org/10.1371/journal.pone.0192010

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title = "Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis",

abstract = "Background Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables. Methods Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO. Results Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO. Conclusion Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.",

author = "Loft, {Nikolai Dyrberg} and Lone Skov and Rasmussen, {Mads Kirchheiner} and Robert Gniadecki and Dam, {Tomas Norman} and Ivan Brandslund and Hoffmann, {Hans J{\"u}rgen} and Andersen, {Malene Rohr} and Dessau, {Ram Benny} and Bergmann, {Ann Christina} and {M{\o}ller Andersen}, Niels and Abildtoft, {Mikkel Kramme} and Andersen, {Paal Skytt} and Hetland, {Merete Lund} and Bente Glintborg and Steffen Bank and Ulla Vogel and Vibeke Andersen",

year = "2018",

doi = "10.1371/journal.pone.0192010",

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T1 - Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis

AU - Loft, Nikolai Dyrberg

AU - Skov, Lone

AU - Rasmussen, Mads Kirchheiner

AU - Gniadecki, Robert

AU - Dam, Tomas Norman

AU - Brandslund, Ivan

AU - Hoffmann, Hans Jürgen

AU - Andersen, Malene Rohr

AU - Dessau, Ram Benny

AU - Bergmann, Ann Christina

AU - Møller Andersen, Niels

AU - Abildtoft, Mikkel Kramme

AU - Andersen, Paal Skytt

AU - Hetland, Merete Lund

AU - Glintborg, Bente

AU - Bank, Steffen

AU - Vogel, Ulla

AU - Andersen, Vibeke

PY - 2018

Y1 - 2018

N2 - Background Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables. Methods Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO. Results Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO. Conclusion Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.

AB - Background Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables. Methods Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO. Results Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO. Conclusion Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.

U2 - 10.1371/journal.pone.0192010

DO - 10.1371/journal.pone.0192010

M3 - Journal article

C2 - 29389950

AN - SCOPUS:85041357741

SN - 1932-6203

VL - 13

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 2

M1 - e0192010

ER -

Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis

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