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Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by a wide spectrum of glandular and extra-glandular features. Genetic and epigenetic factors play an important role in the disease susceptibility and phenotype. There are a multitude of genes that have been identified as implicated in the pathogenesis of pSS, both in HLA and extra-HLA regions with a strong contribution given by genes in interferon signalling pathways. Among the HLA alleles, the most consistent associations have been found with DR2 and DR3 alleles at the DRB1 locus. Moreover, several gene variants outside the MHC locus are in genes involved in NF-κB signalling, B- and T-cell function and methylation processes possibly responsible for lymphomagenesis. There is still a lack of knowledge on precise genetic patterns and prediction models of diseases, and data on pharmacogenetics is scarce. A comprehensive summary of the common genetic factors and an extensive analysis of novel epigenetic aspects is provided, together with a view on the relationships between novel therapeutic agents for pSS and genetic targets in signalling pathways, aiming at improving tailored treatment strategies in the view of a more personalized medicine., Competing Interests: Declaration of competing interest Conflict of interest No funds, grants, or other support were received. The authors have no relevant financial or non-financial interests to disclose. All authors contributed to the study conception and design. All authors read and approved the final manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: Type 2 diabetes (T2D) hyperglycaemia alters basal autophagy. Since autophagy is an essential cellular process, our aim was to investigate the ATG5 (autophagy-related 5) gene expression level and genetic variants in a cohort of diabetic patients, characterized for the presence of microangiopathic complications., Methods and Results: the expression levels of ATG5 were evaluated in PBMCs from 48 T2D patients with an extensive evaluation for microangiopathic complications. Our analyses revealed a significant lower expression of ATG5 in T2D patients with retinopathy compared to those without retinopathy. We also highlighted a significant lower expression of ATG5 in T2D patients with early-cardiovascular autonomic neuropathy compared to those without it, after correction for sex, age, body mass index and levels of hemoglobin A1c., Conclusion: our results highlight that dysregulation in the autophagy process could be involved in the development of severe microangiopathic complications., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Psoriatic Arthritis (PsA) is an immune-mediated rheumatic disease caused by the interaction between environmental factors and genetic predisposition. Many of the risk loci associated with PsA susceptibility are shared with other autoimmune diseases, suggesting an involvement of the same pathways in these diseases. We investigated the association between nine selected polymorphisms and PsA susceptibility and their possible role in the modulation of the disease activity. We analysed 163 patients with PsA and 298 age and sex-matched healthy subjects. Our results showed the associations of five polymorphisms with the disease development: rs33980500 (TRAF3IP2), rs6920220 (TNFAIP3), rs27524 (ERAP1), rs7574865 (STAT4) and rs1800872 (IL10). Patients carrying the variant allele of TRAF3IP2 polymorphism had a higher number of tender/swollen joints and a higher Disease Activity Index for PsA score. The multilocus genetic risk profile showed a higher probability to develop the disease in subjects with at least four risk alleles., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, seen in combination with psoriasis. Both genetic and environmental factors are responsible for the development of PsA, however little is known about the different weight of these two distinctive components in the pathogenesis of the disease. Genomic variability in PsA is associated with the disease and/or some peculiar clinical phenotypes. Candidate genes involved are crucial in inflammation, immune system, and epithelial permeability. Moreover, the genesis and regulation of inflammation are influenced by the composition of the human intestinal microbiome that is able to modulate both mucosal and systemic immune system. It is possible that pro-inflammatory responses initiated in gut mucosa could contribute to the induction and progression of autoimmune conditions. Given such premises, the aim of this review is to summarize immune-mediated response and specific bacterial changes in the composition of fecal microbiota in PsA patients and to analyze the relationships between bacterial changes, immune system, and host genetic background., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases involving a genetically determined inappropriate mucosal immune response towards luminal antigens, including resident bacterial flora. Recent studies identified susceptibility genes involved in autophagy., Aims: We analyzed known autophagic loci (IRGM, ULK1 and AMBRA1) previously described as associated with inflammatory bowel diseases or with other autoimmune and/or inflammatory disorders in a sample of Italian inflammatory bowel diseases patients in order to confirm their possible involvement and relative contribution in the disease., Methods: We performed a case-control association study, a sub-phenotype correlation and a haplotype analysis. The analysis included 263 Crohn's disease, 206 ulcerative colitis patients and 245 matched healthy controls. Five polymorphisms were genotyped by allelic discrimination assays., Results: IRGM was the most strongly associated with Crohn's disease susceptibility [rs13361189: P=0.011, OR=1.66 [95% CI: (1.12-2.45)]; rs4958847: P=0.05, OR=1.43 [95% CI: (1-2.03)]. The SNP rs13361189 was also found to increase the risk of Crohn's disease clinical sub-phenotype (fibrostricturing behaviour, ileal disease, perianal disease, intestinal resection). These findings suggest that IRGM variants may modulate clinical characteristics of Crohn's disease., Conclusions: Our study confirms IRGM rs13361189 and rs4958847 polymorphisms to be important for Crohn's disease susceptibility and phenotype modulation, in accordance with previous findings., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Discrepancies between severity of lesions and symptoms may be observed in Crohn's disease. We prospectively assessed whether Crohn's disease may be diagnosed among asymptomatic relatives of patients, using Small Bowel Contrast Ultrasonography., Methods: Diagnosis of asymptomatic Crohn's disease relatives was defined ultrasonographically as: bowel wall thickness >3mm, bowel dilation/stricture, lumen diameter >2.5 cm. Diagnosis was confirmed by ileocolonoscopy. Subjects were also screened for the Leu3020insC mutation., Results: Consent was given by 35 asymptomatic first-degree relatives of 18 Crohn's disease patients. Ultrasonography indicated increased bowel wall thickness (5mm) compatible with ileal Crohn's disease in 1 relative (2.8%), a 42 year-old male. Ileocolonoscopy, histology, and radiology confirmed the diagnosis of stricturing ileal Crohn's disease. Gallbladder stones were detected in 7/35 (20%) relatives and Leu3020insC mutation in 3/35 (8.5%)., Conclusions: Small Bowel Contrast Ultrasonography may be a useful tool to diagnose asymptomatic small bowel Crohn's disease among first-degree relatives of patients., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Psoriatic arthritis (PsA) has been defined as an inflammatory arthritis associated with psoriasis that may affect as many as 30% of psoriasis patients. Epidemiological study reported strong familial clustering of PsA although the precise etiology of PsA is poorly understood. Recently, a genomewide linkage scan in PsA revealed a LOD score of 2.17 on chromosome 16q and provided strong evidence for a paternal imprinting effect. That region surrounds a psoriasis susceptibility locus including the CARD15 gene which has convincingly been shown to confer susceptibility to Crohn's disease. The existence of a common susceptibility gene for psoriasis/PsA and Crohn disease was recently demonstrated by evidence of association of CARD15 polymorphisms with PsA. To confirm these results in an independent population, we analyzed a data set of 193 Italian PsA patients and 150 controls for CARD15 polymorphisms (R702W, G908R and leu1007finsC) previously demonstrated associated with PsA. Here we report no evidence for association in the examined population for CARD15 polymorphisms, suggesting that the positive association previously reported in a genetically isolated population was the result of a linkage disequilibrium due to a founder effect.

Both in diabetic and in normal pregnancy the proportion of macrosomic fetuses is much lower among newborns carrying Pc allele of erythrocyte acid phosphatase (ACP1) than among other ACP1 genotypes. In diabetic pregnancy the well known increased incidence of fetal macrosomia has been observed only among fetuses which do not carry this allele. ACP1 probably functions as a flavin-mononucleotide phosphatase. Since Pc allele is associated with the highest enzymatic activity it is likely that subjects carrying this gene may have a relatively lower concentration of flavin-mononucleotide cofactors and in turn a reduced rate of metabolic activities controlled by flavoenzymes. It is possible that in fetuses carrying Pc, flavo-enzyme activities are regulated at a level that does not allow a full response to stimuli (both genetic and/or environmental) aimed to maximize fetal growth.