The Role of Osteopontin OPN-SPP1 Haplotypes in the Susceptibility to Crohns DiseaseReportar como inadecuado

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Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease IBD. The aim of our study was to analyze the association of osteopontin OPN-SPP1 gene variants in a large cohort of IBD patients.

Methodology-Principal Findings

Genomic DNA from 2819 Caucasian individuals n = 841 patients with Crohn-s disease CD, n = 473 patients with ulcerative colitis UC, and n = 1505 healthy unrelated controls was analyzed for nine OPN SNPs rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138. Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs rs4754, rs1126616, rs1126772 and rs9138, we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients p = 0.0004, OR = 0.69. None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 omnibus p-value = 2.07×10−8. Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles p = 3.66×10−5. There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 p = 4.18×10−2 and between OPN SNP rs1126616 and IL23R SNP rs2201841 p = 4.18×10−2 but none of these associations remained significant after Bonferroni correction.


Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion.

Autor: Jürgen Glas , Julia Seiderer , Corinna Bayrle, Martin Wetzke, Christoph Fries, Cornelia Tillack, Torsten Olszak, Florian Beigel,



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