1. Introduction. Multiple cytokines have been studied for their role in the propagation of the inflammatory process related to inflammatory bowel diseases (IBD), but the role of interleukin-4 remains controversial. The aim of this study was to evaluate the role of two IL-4 gene single nucleotide polymorphisms (SNPs) in disease susceptibility and phenotypic expression. 2. Materials and Methods. A group of 160 patients with IBD (86CD/74UC) and 160 healthy controls were genotyped for IL-4 rs2243250/−590C/T and rs2070874/−34C/T using real-time polymerase chain reaction with TaqMan assay. 3. Results. The analysis of IBD patients and controls revealed a significantly reduced frequency of the minor allele T of both SNPs in CD patients (p = 0.03, OR 0.55 and p = 0.02, OR 0.52) and for the entire IBD group (p = 0.01, OR 0.57 and p = 0.01, OR 0.55). Haplotype analysis identified the most frequent haplotype (rs2243250/rs2070874 CC) associated with a high risk for developing IBD (either UC or CD) (p = 0.003). IBD patients with extraintestinal manifestations had significantly increased frequency of the minor alleles T. We also found an association between the presence of allele C of rs2070874 and response to antiTNF treatment. 4. Conclusions. This is the first study to investigate the IL-4 gene’s relation to IBD susceptibility conducted in Romania. Both SNPs were found to be associated with disease susceptibility and phenotypic features, such as extraintestinal manifestations and response to antiTNF agents.

Background and objectives: One of the most frequent glomerular diseases in the pediatric population is represented by the idiopathic nephrotic syndrome (INS). The exact mechanisms mediating the disease are still unknown, but several genetic factors have been studied for possible implications. Cytokines are considered to play a pivotal role in mediating INS disease progression, interleukin-4 (IL-4) exhibiting particular interest. The objective of this research project was to investigate the association between two IL-4 gene single-nucleotide polymorphisms (SNPs) and INS susceptibility as well as response to steroid therapy, in a group of Romanian children. Materials and Methods: In total, 75 patients with INS and 160 healthy controls of Romanian origin were genotyped for IL-4 rs2243250/−590C/T and rs2070874/−34C/T using real-time polymerase chain reaction. Association tests were performed using the DeFinetti program and Plink 1.07 software and p-values < 0.05 were considered statistically significant. Results: The analysis of INS patients and controls revealed a similar genotype distribution of the studied SNPs. The minor T alleles were less frequent in the INS group, but not statistically significant (p = 0.1, OR = 0.68 and p = 0.2, OR = 0.74). Regarding the response to steroids, a low frequency of 590*T allele in steroid-resistant patients (7.7%), compared with steroid-sensitive patients (14%) and controls (17.5%), was obtained, but the difference did not reach the statistical significance threshold. The same result was obtained for −34C/T SNP. Conclusions: This is the first study examining the relationship between the IL-4 gene and INS susceptibility conducted in a European population, and particularly in Romania. The investigated SNPs were found to not be associated with disease susceptibility or response to the steroid treatment of pediatric INS.

Background/Objectives: Tumor necrosis factor alpha (TNF-alpha) plays a key role in systemic inflammation in multiple disorders, including inflammatory bowel diseases (IBDs). Our purpose was to investigate the contribution of two promoter single-nucleotide polymorphisms (rs361525/–238G/A and rs1800629/–308G/A) to disease susceptibility, clinical features, and response to biologic therapy in a cohort of Romanian patients with IBDs. Methods: A total of 198 patients with IBDs, 106 with Crohn’s disease (CD) and 92 with ulcerative colitis (UC), as well as 160 healthy controls, all Caucasians of Romanian origin, were genotyped using TaqMan Allelic Discrimination Assays. Phenotypical and anti-TNF treatment characteristics of the patients with IBDs were recorded. Statistical analyses were performed using OpenEpi and PLINK v1.07 software. Results: We found a significantly higher frequency of the minor allele A of rs361525 in patients with CD than in the controls (6.6% vs. 2.2%, p = 0.01, OR = 3.16). Half of the patients with extraintestinal manifestations (EIMs) had at least one copy of the rs1800629 A allele compared with approximately 10% of patients without EIM (p = 1 × 10⁻⁴, OR 9.58 for UC and p = 9 × 10⁻⁴, OR 6.60 for CD). In the whole IBD group of patients, the carriers of the minor allele (AA+GA) for both SNPs studied (rs1800629 and rs361525) were significantly more likely to have EIM associated with IBDs (p = 3 × 10⁻⁷, OR 7.87; p = 0.03, OR 3.02, respectively). In patients with UC, the analysis according to disease extension revealed that the frequency of the minor allele of rs1800629 was significantly higher in the subgroup with the E2 phenotype compared to the E1 and E3 phenotypes (16.6% versus 5.6%, p = 0.02, OR 3.32). Conclusions: These findings highlight the role of genetic TNF-alpha variants in disease susceptibility, phenotype, and systemic involvement, supporting their potential relevance in understanding IBD heterogeneity.

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Representing a pathology frequently encountered in the clinical pediatric practice, non-IgE-mediated food allergy is characterized by delayed immune-mediated adverse reactions to foods. Various genetic and environmental factors play complex and incompletely elucidated roles in the development of this type of allergic pathology. In the present research, we aimed to assess the associations of the TSLP gene single-nucleotide polymorphisms (SNPs) rs3806933 and rs10062929 with the risk of non-IgE-mediated food allergy, as well as with other characteristics of these patients. The study included 87 Romanian patients with non-IgE-mediated food allergy and 115 healthy controls. The two SNPs were genotyped using Real-Time PCR TaqMan Allelic Discrimination Assays. No associations were identified between rs3806933 or rs10062929 and the risk of non-IgE-mediated food allergy. The frequency of the minor allele C of rs3806933 was lower in children with atopic dermatitis (35.4% vs. 46.8%), a positive family history of atopic disease (39.0% vs. 47.8%), and elevated levels of total IgE (39.2% vs. 45.7%), but not statistically significant.

Background: Non-infectious uveitis (NIU) is an inflammatory ocular condition often associated with systemic immune-mediated disorders. The pathogenesis of NIU is complex and involves genes from the Human Leukocyte Antigen (HLA) class I system. Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves antigenic peptides to an optimal length for loading and presentation on HLA I molecules. In this systematic review, we aimed to summarize the current knowledge regarding how susceptibility to developing NIU is linked to single-nucleotide polymorphisms (SNPs) in the ERAP1 gene, a locus well known for its connection to autoinflammatory disorders. Methods: We performed a PRISMA protocol-guided systematic review in various databases. Results: Out of the 311 screened studies, only 12 met the inclusion criteria. Five of them are Genome-Wide Association Studies. We found relevant research for three types of NIU: acute anterior uveitis, Behçet’s uveitis, and birdshot chorioretinopathy. A frequently observed association between ERAP1 SNPs and disease risk was noted when analyzing the HLA-carriers (B*27, B*51, A*29), which points toward an epistatic interaction between ERAP1 and the MHC class I complex. Conclusions: Our findings suggest that ERAP1 gene variation is understudied in relation to NIU. A significant amount of research has also concentrated on risk stratification, and reliable markers for patient selection are needed, especially in view of emerging anti-ERAP therapies.