Expression patterns common and unique to ulcerative colitis and celiac disease
ANNALS OF HUMAN GENETICS
Authors: Maria Medrano, Luz; Pascual, Virginia; Bodas, Andres; Lopez-Palacios, Natalia; Salazar, Isabel; Espino-Paisan, Laura; Gonzalez-Perez, Beatriz; Urcelay, Elena; Luis Mendoza, Juan; Nunez, Concepcion
Abstract
Autoimmune diseases like celiac disease (CeD) and ulcerative colitis (UC) show a common genetic background defined by the existence of shared susceptibility loci. We aimed to go deeper into this common genetic background through performing a cross-disease study based on gene expression. We measured the expression of 21 genes located in 13 CeD-UC susceptibility regions, and 10 genes in five CeD risk regions. Determinations were carried out in colon/rectum samples from 13 UC patients (inflamed and uninflamed tissue) and four colon samples from controls. Duodenal samples from 19 CeD patients and 12 controls were used for comparisons. Differences were analyzed using the Bayesian method. The shared chromosomal regions containing TNFAIP3, PTPN2, ICOSLG, C1orf106, and IL21 showed similar results in both diseases. FASLG, PLEK, CCR4, and TAGAP, all located in CeD risk loci, were up-regulated in both CeD and UC patients. Finally, ZFP36L1, ZMIZ1, PUS10, UBE2L3, and BACH2 showed opposite results in CeD and UC. A high complexity underlies autoimmune common susceptibility loci, as the expression pattern of the studied genes does not always correlate with the one expected attending to the apparent genetic background. Differentially expressed genes such as ZFP36L1, ZMIZ1, PUS10, and BACH2 deserve further research in autoimmune diseases.
Gene-gene interactions in IL23/Th17 pathway contribute to psoriasis susceptibility in Chinese Han population
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Authors: Wang, W. -J.; Yin, X. -Y.; Zuo, X. -B.; Cheng, H.; Du, W. -D.; Zhang, F. -Y.; Yang, S.; Zhang, X. -J.
Abstract
Background Psoriasis is a common chronic inflammatory skin disease. IL23/Th17 is a newly confirmed pathway in psoriasis. Objective To investigate the gene-gene interactions in IL23/Th17 pathway underlying psoriasis. Methods A total of 299 single-nucleotide polymorphisms from 11 genes in IL23/Th17 pathway were genotyped on 1139 patients with psoriasis and 1694 controls. Multifactor dimensionality reduction and logistic regression algorithms were applied to explore the gene-gene interactions. Results We found that there were a three-way interaction among IL21, CCR4 and TNF(chi(2) = 5.02(1), P = 0.025) and three pair-wise gene-gene interactions between IL12RB1 and CCR4(chi(2) = 11.66(4), P = 0.0201), IL22 and CCR4 (chi(2) = 11.97(4), P = 0.0176), IL12RB1 and IL6 (chi(2) = 7.31(1), P = 0.0069) in psoriasis. Conclusions Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis.