Association between single nucleotide polymorphisms in prospective genes and susceptibility to ankylosing spondylitis and inflammatory bowel disease in a single centre in Turkey

Küçükşahin, Orhan; Ateş, Aşkın; Türkçapar, Nuran; Törüner, Murat; Turgay, Murat; Duman, T.; Şahin, Ali; Yıldızgören, Mustafa Turgut; Okoh, Alexis K.; Kulahcioglu, Emre; Erten, Şükran; Kınıklı, Gülay; Assadpour, Saeid; Düzgün, Nurşen

doi:10.5152/tjg.2016.15466

Cited by 17 publications

(9 citation statements)

References 16 publications

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“…There is no information in literature about a similar association of any known genetic variant with age of diagnosis of NSCLC, therefore these observations need further development. Interestingly, rs26653 in ERAP1 has been associated with several autoimmune diseases including psoriasis (62)(63)(64), ankylosing spondylitis and inflammatory bowel disease (65). This information indicates that rs26653 may be functional.…”

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confidence: 88%

Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers

et al. 2021

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Lung cancer is strongly associated with cigarette smoking; nevertheless some never-smokers develop cancer. Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components. We have already published highly significant associations of single nucleotide polymorphisms (SNPs) of the ERAP1 gene with non-small cell lung cancer (NSCLC) in Chinese, but not in Polish populations. However, the smoking status of participants was not known in the previous study. Here, we compared the distribution of APM polymorphic variants in larger cohorts of Polish patients with NSCLC and controls, stratified according to their smoking status. We found significant but opposite associations in never-smokers and in smokers of all tested SNPs (rs26653, rs2287987, rs30187, and rs27044) but one (rs26618) in ERAP1. No significant associations were seen in other genes. Haplotype analysis indicated that the distribution of many ERAP1/2 haplotypes is opposite, depending on smoking status. Additionally, haplotypic combination of low activity ERAP1 and the lack of an active form of ERAP2 seems to favor the disease in never-smokers. We also revealed interesting associations of some APM polymorphisms with: age at diagnosis (ERAP1 rs26653), disease stage (ERAP1 rs27044, PSMB9 rs17587), overall survival (ERAP1 rs30187), and response to chemotherapy (ERAP1 rs27044). The results presented here may suggest the important role for ERAP1 in the anti-cancer response, which is different in smokers versus never-smokers, depending to some extent on the presence of ERAP2, and affecting NSCLC clinical course.

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confidence: 88%

Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers

et al. 2021

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“…Interestingly, SNP rs26653 was significantly associated with NSCLC in the Chinese population [ 22 ], and recently also in Polish Caucasians after adjusting for smoking status [ 10 ]. In addition, several previous reports have linked it to some autoimmune diseases, including psoriasis [ 23 – 25 ], ankylosing spondylitis, and inflammatory bowel disease [ 26 ]. The association of rs26653 with the disorders mentioned above indicates that it may functionally affect the enzymatic properties of ERAP1, and/or influence gene expression level.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer

et al. 2023

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Background ERAP1 is a major aminopeptidase that serves as an editor of the peptide repertoire by trimming N-terminal residues of antigenic peptides, creating a pool of peptides with the optimal length for MHC-I binding. As an important component of the antigen processing and presenting machinery – APM, ERAP1 is frequently down-regulated in many cancers. Since ERAP1 expression has not yet been thoroughly investigated in non-small cell lung cancer (NSCLC), we decided to analyze ERAP1 mRNA levels in tissues collected from NSCLC patients. Methods Using real-time qPCR, we evaluated ERAP1 mRNA expression in samples of tumor and adjacent non-tumor tissue (serving as control tissue) from 61 NSCLC patients. Results We observed a significantly lower level of ERAP1 mRNA expression in tumor tissue (MedTumor = 0.75) in comparison to non-tumor tissue (MedNon-tumor = 1.1), p = 0.008. One of the five tested polymorphisms, namely rs26653, turned out to be significantly associated with ERAP1 expression in non-tumor tissue (difference [d] = 0.59 CI95% (0.14;1.05), p = 0.0086), but not in tumor tissue. The levels of ERAP1 mRNA expression did not affect the overall survival of NSCLC patients, either in the case of the tumor (p = 0.788) or in non-tumor (p = 0.298) tissue. We did not detect any association between mRNA ERAP1 expression level in normal tissue and: (i) age at diagnosis (p = 0.8386), (ii) patient’s sex (p = 0.3616), (iii) histological type of cancer (p = 0.7580) and (iv) clinical stage of NSCLC (p = 0.7549). Furthermore, in the case of tumor tissue none of the abovementioned clinical parameters were associated with ERAP1 expression (p = 0.76). Conclusion Down-regulation of ERAP1 mRNA observed in NSCLC tissue may be related to tumor immune evasion strategy. The rs26653 polymorphism can be considered an expression quantitative trait locus (eQTL) associated with ERAP1 expression in normal lung tissue.

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“…Finally, the examined structural nucleotide changes do not invariably lead to the postulated consequences for gene expression and/or protein function ( 17 ). AS is a genetically diverse condition and despite statistical associations reported for individual SNPs, a more complex interplay of multiple genetic alterations may be required to not only create an environment suited to disease development, but also to underwrite the diversity of the clinical disease ( 18, 19 ).…”

Section: Discussionmentioning

confidence: 99%

IL-1A gene variation in relation to cytokine levels and clinical characteristics in ankylosing spondylitis

2019

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Objective Variations in the IL-1 alpha (IL-A) gene increase the risk for ankylosing spondylitis (AS), but the pathway underlying this association is not fully understood. As IL-1A is primarily a regulatory cytokine, we investigated the influence of IL-1A gene variation on disease severity and cytokine expression in AS. Methods This was a cross sectional study of tumor necrosis factor inhibitors (TNFi)-naïve AS patients (n=334, 90% B27 +, age 45 years) fulfilling the modified New York criteria. We recorded demographics, clinical findings, spinal mobility, Bath AS Functional Index (BASFI), and routine lab findings. IL-1A genotyping for three AS-associated single nucleotide polymorphism (SNP; rs2856836, rs17561 and rs1894399) was performed using Taqman RT-PCR, with TNF, IL-6, IL-17A, and IL-23 levels measured using ELISA. Genotypic associations included logistic regression analysis for genotype (codominant model) and global haplotype (threshold 5%) associations with cytokine levels and clinical features. Results The three variants were in near complete linkage disequilibrium and formed two only common haplotypes (ACC 67%, GAT 33%). The levels for TNF, IL-6, IL-17A, IL-23, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were similar across genotypes and haplotypes (all p-values >0.4) as were the measures for spinal mobility and BASFI. The TAQ haplotype showed a borderline significant trend with reduced heart disease and mortality during follow-up. Conclusion IL-1A gene cluster variations do not have an impact on the clinical disease measures or cytokine levels in AS, suggesting that IL-1A has no direct role in AS.

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Association between single nucleotide polymorphisms in prospective genes and susceptibility to ankylosing spondylitis and inflammatory bowel disease in a single centre in Turkey

Cited by 17 publications

References 16 publications

Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers

Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers

Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer

IL-1A gene variation in relation to cytokine levels and clinical characteristics in ankylosing spondylitis

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