A deletion atADAMTS9-MAGI1locus is associated with psoriatic arthritis risk

MAGI1 as a link between endothelial activation and ER stress drives atherosclerosis

“…In the present study, we found that MAGI1 is essential for NF-κB activation in ECs induced by various proinflammatory stimuli. While it remains unclear whether a single-nucleotide polymorphism or deletion close to the MAGI1 gene as previously reported (4,5) can increase MAGI1 expression in humans, our study demonstrates that both PTMs and expression of MAGI1 have a significant effect on EC activation as well as atherosclerotic plaque formation. Further studies are necessary to determine whether the single-nucleotide polymorphism in the first intron of Magi1 or the intergenic deletion between the Adamts9 and Magi1 genes at the chromosome 3p14.1 locus can change MAGI1 expression or PTMs in ECs and/or epithelial cells.…”

“…In particular, d-flow, which is known to occur in so-called atheroprone areas of large arteries, activates proinflammatory and apoptotic signaling in ECs, leading to EC dysfunction (1,2). A recent genome-wide association study of an independent cohort of patients with various diseases and healthy controls revealed a possible association between the membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1) locus and the severity of several chronic inflammatory diseases, such as inflammatory bowel disease (IBD), psoriasis, and neuroticism (3)(4)(5)(6). Concordantly, MAGI1 mRNA expression levels in small intestine mucosa are increased in patients with IBD (3).…”

Genome-wide association and targeted analysis of copy number variants with psoriatic arthritis in German patients

“…Of note, we did not detect association to the CNVs at previously identified copy number loci such as LCE3C / LCE3B [ 5 ], the ß-defensin-cluster [ 19 , 20 ] and the intergenic deletion [ 25 ]. As we had not observed association to the LCE3C / LCE3B in a largely overlapping cohort of 650 German PsA patients [ 34 ], we did not expect to find evidence for association.…”

“…Although CNVs have been shown to potentially play a role in the genetic basis of both PsV and PsA [ 5 , 19 , 20 , 22 , 25 ], our GWAS of CNVs failed to identify any novel disease-associated CNV for PsA. As a result of our three-stage analysis comprising thorough quality assessment [ 27 ], validation by MLPA as a second quantitative method and replication analysis in an enlarged case-control study, none of the originally identified disease-associations of CNVs remained significant.…”

“…In addition, a frequent 32 kb deletion within the late cornified envelope 3 gene cluster ( LCE3C_3B-del ) was found to be a risk factor for both PsV and PsA [ 5 , 21 – 24 ]. More recently an intergenic deletion has been shown to be associated with PsA, but not with PsV [ 25 ].…”