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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (<i>P</i> < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: <i>TNF</i> (rs361525) was associated with PsO, PsC10, and PsA; and <i>IL12B</i> (rs6887695) was associated with PsO.</p><p>Conclusion</p><p>Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the <i>IL12B</i> and <i>TNF</i> genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.</p></div

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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (<i>P</i> < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: <i>TNF</i> (rs361525) was associated with PsO, PsC10, and PsA; and <i>IL12B</i> (rs6887695) was associated with PsO.</p><p>Conclusion</p><p>Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the <i>IL12B</i> and <i>TNF</i> genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.</p></div

Risk estimates for carriers of the variant allele compared to homozygous carriers of the wild type allele.

<p>Risk estimates for carriers of the variant allele compared to homozygous carriers of the wild type allele.</p

Characteristics and demographics of patients with psoriasis, psoriatic arthritis, cutaneous only psoriasis, and healthy controls.

<p>Characteristics and demographics of patients with psoriasis, psoriatic arthritis, cutaneous only psoriasis, and healthy controls.</p

Minimum effect size in which we had > 80% power at 5% significance level and a minor allele frequency (MAF) of 0.05, 0.25, and 0.45 for each phenotype.

<p>Minimum effect size in which we had > 80% power at 5% significance level and a minor allele frequency (MAF) of 0.05, 0.25, and 0.45 for each phenotype.</p

Description of the study participants.

<p>Description of the study participants.</p

The biologic effect of the studied single nucleotide polymorphism (SNP) and odds ratios (OR) for polymorphisms which have been shown to be associated with risk of Crohn's disease (CD), ulcerative colitis (UC) or inflammatory bowel disease (IBD) in previous studies and in this study.

A<p>Crude (unadjusted).</p>B<p>Adjusted for age, gender and smoking status.</p>C<p>Function examined by flow cytometry.</p>D<p>Function examined by luciferase reporter assay.</p>E<p>Function examined by enzyme-linked immunosorbent assay (ELISA).</p>F<p>Function examined by reverse transcriptase PCR (RT-PCR).</p>G<p>Function examined by electrophoretic mobility shift assay (EMSA).</p><p>ND: not determined.</p

Sixteen functional single nucleotide polymorphisms (SNPs) in 13 genes involved in regulation of inflammation were found to be associated with susceptability of severe Crohn's disease (CD), ulcerative colitis (UC) or inflammatory bowel diseases (IBD).

<p>Eleven of the SNPs have not previously been reported as susceptability polymorphisms of CD, UC or IBD (<i>TLR2</i> (rs4696480 and rs1816702), <i>TLR4</i> (rs1554973 and rs12377632), <i>TLR9</i> (rs187084 and rs352139), <i>LY96</i> (rs11465996), <i>NFKBIA</i> (rs696), <i>TNFRSF1A</i> (rs4149570), <i>IL6R</i> (rs4537545) and <i>PTPN22</i> (rs2476601)).</p