Genome-Wide Meta-Analysis in Alopecia Areata Resolves HLA Associations and Reveals Two New Susceptibility Loci

Alopecia areata (AA) is a prevalent autoimmune disease with ten known susceptibility loci. Here we perform the first meta-analysis in AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the MHC, where we fine-map 4 independent effects, all implicating HLA-DR as a key etiologic driver. Outside the MHC, we identify two novel loci that exceed statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, TGFß/Tregs and JAK kinase signaling, and support the causal role of aberrant immune processes in AA

Do dental procedures affect lung function and arterial oxygen saturation in asthmatic patients?

Background: Asthma is a chronic inflammatory condition of the airways. Pain and anxiety triggered by dental treatment can induce the secretion of endogenous catecholamines. When the situation is combined with the use of local anesthetics with vasoconstrictors, it may increase its undesirable effects on the cardiovascular system and respiratory systems. Aim of the work: To evaluate the effects of dental procedures with and without local anesthesia on pulmonary function and arterial oxygen saturation in healthy volunteers and asthmatic patients. Patients and methods: Our study included 30 asthmatic patients, and 20 healthy volunteers. Careful history taking, clinical examination, spirometry and pulse oximetry to measure O2 saturation before and 10 min after dental procedures were obtained. Results: Pulmonary function showed a statistically significant decrease in PEF and O2 saturation in asthmatic patients and a statistically significant decrease in O2 saturation in the healthy group after dental procedures compared to pre-procedure results. Asthmatic patients receiving local anesthesia had a statistically significant decrease in PEF and O2 saturation after dental procedures compared to pre-procedure results. In the healthy group, there was a statistically significant decrease in O2 saturation after dental filling and dental prosthesis and in asthmatic patients after dental filling, extraction, prosthesis, and scaling compared to that before. Conclusion: Asthmatic patients may be at a higher risk of developing oxygen desaturation after dental procedures regardless of their type with and without local anesthesia and a decrease in PEF after dental procedures with local anesthesia

Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci

Alopecia areata (AA) is a prevalent autoimmune disease with ten known susceptibility loci. Here we perform the first meta-analysis in AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the MHC, where we fine-map 4 independent effects, all implicating HLA-DR as a key etiologic driver. Outside the MHC, we identify two novel loci that exceed statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, TGFß/Tregs and JAK kinase signaling, and support the causal role of aberrant immune processes in AA