Mostafa Saadat

Background/aim: Given that phosphorylation/dephosphorylation of many important proteins at tyrosine residues play a vital role in various cellular functions, it can be inferred that protein tyrosine phosphatase enzymes, including the protein tyrosine phosphatase non-receptor type 13 ( PTPN13 ), are involved in numerous critical cellular processes. PTPN13 influences several signaling pathways and biological activities, suggesting a potential role in carcinogenesis. This study aimed to select the most relevant PTPN13 polymorphism using “polymorphism selection index” (PSI) and investigate its association with gastric (GC) and colorectal (CRC) cancer risk. Methods: Missense polymorphisms with minor allele frequency ≥ 0.01 were retrieved and PSI was calculated for each. We conducted two case-control studies in an Iranian population (197 CRC/215 controls; 150 GC/230 controls). Genotyping was carried out by PCR-RFLP. Associations with cancer risk were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Results: Among seven missense polymorphisms, rs989902 (T > G, Y2081D) had the highest PSI and was selected. Consequently, we focused on investigating the association between this polymorphism and the risk of CRC and GC. The GG genotype was found to increase the risk of both cancers (for CRC: OR = 2.36, 95% CI = 1.18–4.69, p = 0.014; for GC: OR = 2.14, 95% CI = 1.06–4.31, p = 0.033). Conclusion: This study demonstrates that the rs989902 is significantly associated with the risk of CRC and GC in an additive manner. Furthermore, the cancer risk elevated with an increasing number of combined risk factors, including the rs989902-GG genotype, smoking, and family history of cancer, highlighting the importance of this genetic variant in the etiology of these malignancies.

By Mostafa Saadat, Published on 02/14/26

Aim: Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving both genetic and environmental factors. A 32-bp deletion polymorphism (Δ32, rs333) in the C-C chemokine receptor type 5 ( CCR5 ; MIM: 601373) results in a non-functional receptor and alters immune-related gene expression, suggesting its potential role in SLE pathogenesis. However, findings from previous studies have been inconsistent. This meta-analysis therefore aimed to clarify the association between the rs333 and susceptibility to SLE by synthesizing all available genetic data. Methods: This study was conducted in accordance with the PRISMA guidelines. Eligible studies were identified by searching ten databases. Three genetic models (heterozygous, dominant, and allelic) were analysed using random- or fixed-effects models based on heterogeneity assessments. The wt/wt genotype and wt allele served as references. Results: The initial search of the databases yielded 124 articles. Ultimately, eight case-control studies involving 1323 SLE patients and 1724 controls were included. No significant association was found between the CCR5 -Δ32 variant and SLE risk in any genetic model (heterozygous: OR = 0.95, 95% CI: 0.58–1.54, p = 0.851; dominant: OR = 0.99, 95% CI: 0.60–1.65, p = 0.989; allelic: OR = 1.03, 95% CI: 0.62–1.70, p = 0.889), despite significant heterogeneity between studies (I²=68.8–74.4%). No evidence of publication bias was found. Conclusion: Despite strong biological plausibility, this meta-analysis found no significant association between the rs333 and susceptibility to SLE, a finding consistent with null results reported in multiple sclerosis. Although limitations of the included studies preclude definitive conclusions, the cumulative evidence suggests that the rs333 is unlikely to be a primary genetic determinant of SLE risk.

The Article Abstract is not available

Psoriasis is a chronic autoimmune skin disease that has been associated with many polymorphic genes based on genome-wide association studies (GWAS). To perform gene ontology and biological pathway analysis of genes associated with psoriasis and also to investigate the degree of commonality of psoriasis-associated loci with susceptibility loci of some other autoimmune diseases, a total of 319 psoriasis-associated polymorphic protein-coding genes were included in the analysis. The web-based Enrichr was used for performing present analysis. Cytokine-cytokine receptor interaction and JAK-STAT signaling were predicted by KEGG analysis. The top biological process and molecular function were positive regulation of cytokine production and cytokine receptor activity, respectively. The present findings revealed that the psoriasis-associated genes were significantly involved in the immune system and its functions, consistent with the autoimmune nature of the disease. The present study revealed that there were 10 genes shared between psoriasis and other 5 autoimmune diseases, interestingly, these genes were significantly enriched in the JAK-STAT pathway (adjusted p-value = 3.75e-5). There were several multifactorial diseases and complex traits that had a statistically significant commonality between their predisposing genes and psoriasis predisposing genes. The current findings suggest that the JAK-STAT pathway is likely involved in the pathogenesis of psoriasis, such as many other autoimmune diseases. Therefore, it is suggested that inhibitors that block the gene transcription of pro-inflammatory cytokines by blocking intracellular signaling pathways mediated by JAK-STAT may be a good model for the treatment of autoimmune diseases, including psoriasis.