ANXA11 rs1049550 Associates with Löfgren’s Syndrome and Chronic Sarcoidosis

Abstract

Sarcoidosis is an immune mediated granulomatous disease commonly affecting the lungs. Genome wide association studies identified many genomic regions that are shared among multiple immune mediated diseases. However, ANXA11 gene polymorphism rs1049550 is exclusively associated with sarcoidosis, making it a key gene of interest for sarcoidosis disease pathogenesis. However, sarcoidosis is a heterogeneous disease and contradictory findings for ANXA11 have been reported for disease phenotypes. We performed a case–control association study to investigate if ANXA11 associates with benign (Löfgren’s syndrome (LS)) or chronic sarcoidosis and performed a meta-analysis on previously reported findings. A total of 262 sarcoidosis patients, of which 149 had LS and 113 chronic sarcoidosis, and 363 controls were genotyped for rs1049550. Meta-analysis included allele findings for rs1049550 from 6 additional studies. We found a significantly lower T allele frequency in sarcoidosis patients than in healthy controls (0.30 vs. 0.41, respectively, odds ratio (OR) 0.61, 95% confidence interval (CI) 0.48–0.77, p = 3 × 10−5). In LS the T allele frequency of 0.33, and in chronic sarcoidosis the T allele frequency of 0.26 were significantly lower than in healthy controls (OR 0.69, 95% CI 0.52–0.92, p = 0.01 and OR 0.51, 95% CI 0.36–0.70, p = 4 × 10−5, respectively). Meta-analysis including previously published European, African American and Asian cohorts confirmed the association of rs1049550 with sarcoidosis and resulted in a pooled OR of 0.70 (CI 0.66–0.75, p = 3.58 × 10−29). Presence of the T allele of rs1049550 in ANXA11 is protective for sarcoidosis, including benign and chronic phenotypes of the disease.

DNA methylation fine-tunes pro-and anti-inflammatory signalling pathways in inactive ulcerative colitis

“…Two other speci cally hypo-methylated genes in inactive UC of relevance for IBD include ANAX11 and lncRNA AFAP1-AS1. ANXA11 has been shown to be a sarcoidosis susceptibility gene (Karakaya et al 2022). An association between sarcoidosis and ulcerative colitis has been reported (Fries et al 1995).…”

Exome Sequencing Reveals Genetic Variability and Identifies Chronic Prognostic Loci in Chinese Sarcoidosis Patients

“…Most of the genes were related to T-cell regulation and T-cell activation during antigen presentation by APCs (antigen-presenting cells) (5). Other genes associated with immune regulation of sarcoidosis, including NOTCH4, TNFa, NOD2, and ANXA11, were also detected by GWAS analysis in different races (28)(29)(30)(31). Multiple factors, including genetic composition and the context of antigen presentation, could impact the inflammatory immune response, resulting in a selflimiting or a chronic relapse type of sarcoidosis prognosis.…”

From Karl Wurm and Guy Scadding's staging to 18F-FDG PET/CT scan phenotyping and far beyond: perspective in the evading history of phenotyping in sarcoidosis

“…GWASs provide insight into phenotypic biology, predict clinical outcomes, and reveal causal relationships between risk factors and health outcomes. Recent GWAS in European, African American, and Asian populations identified a non-synonymous single-nucleotide polymorphism (SNP), rs1049550, within the annexin A11 (ANXA11) gene as being associated with susceptibility to sarcoidosis ( 95 ). The RNA-sequencing (RNA-seq) technologies, such as bulk and single-cell RNA-sequencing (scRNA-seq), permit unbiased interrogation of the whole transcriptome and deep immunophenotyping of heterogeneous single cells suspensions, respectively.…”