YKL-40 is a local marker for inflammation in patients with pseudoexfoliation syndrome

Gönen, Tansu; Güzel, Savaş; Keskinbora, Hıdır Kadircan

doi:10.1038/s41433-018-0308-8

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…The association with inflammation is consistent with studies in limited numbers of XFS patients that found elevated inflammatory markers relative to controls, including cytokines, and markers such as interleukin-6 (IL-6) and IL-8 [70,71], tumor necrosis factor-α (TNFα) and YKL-40 [72,73]. However, there are conflicting results for high sensitivity C-reactive protein [74,75].…”

Section: Discussionsupporting

confidence: 81%

Analysis of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome

et al. 2023

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Background Exfoliation syndrome (XFS) is an age-related systemic disorder characterized by excessive production and progressive accumulation of abnormal extracellular material, with pathognomonic ocular manifestations. It is the most common cause of secondary glaucoma, resulting in widespread global blindness. The largest global meta-analysis of XFS in 123,457 multi-ethnic individuals from 24 countries identified seven loci with the strongest association signal in chr15q22–25 region near LOXL1. Expression analysis have so far correlated coding and a few non-coding variants in the region with LOXL1 expression levels, but functional effects of these variants is unclear. We hypothesize that analysis of the contribution of the genetically determined component of gene expression to XFS risk can provide a powerful method to elucidate potential roles of additional genes and clarify biology that underlie XFS. Results Transcriptomic Wide Association Studies (TWAS) using PrediXcan models trained in 48 GTEx tissues leveraging on results from the multi-ethnic and European ancestry GWAS were performed. To eliminate the possibility of false-positive results due to Linkage Disequilibrium (LD) contamination, we i) performed PrediXcan analysis in reduced models removing variants in LD with LOXL1 missense variants associated with XFS, and variants in LOXL1 models in both multiethnic and European ancestry individuals, ii) conducted conditional analysis of the significant signals in European ancestry individuals, and iii) filtered signals based on correlated gene expression, LD and shared eQTLs, iv) conducted expression validation analysis in human iris tissues. We observed twenty-eight genes in chr15q22–25 region that showed statistically significant associations, which were whittled down to ten genes after statistical validations. In experimental analysis, mRNA transcript levels for ARID3B, CD276, LOXL1, NEO1, SCAMP2, and UBL7 were significantly decreased in iris tissues from XFS patients compared to control samples. TWAS genes for XFS were significantly enriched for genes associated with inflammatory conditions. We also observed a higher incidence of XFS comorbidity with inflammatory and connective tissue diseases. Conclusion Our results implicate a role for connective tissues and inflammation pathways in the etiology of XFS. Targeting the inflammatory pathway may be a potential therapeutic option to reduce progression in XFS.

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Section: Discussionsupporting

confidence: 81%

Analysis of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome

et al. 2023

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“…68,69 The association with inflammation is consistent with studies in limited numbers of XFS patients that found elevated inflammatory markers relative to controls, including cytokines, and markers such as interleukin-6 (IL-6) and IL-8, 70,71 tumor necrosis factor-α (TNF-α) and YKL-40. 72,73 However, there are conflicting results for high sensitivity C-reactive protein. 74,75 16 In addition, the XFS gene sets are enriched for genes that map to variants implicated in coffee and caffeine intake.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Etiology of Exfoliation Syndrome

Hirbo

Pasutto

Gamazon

et al. 2020

Preprint

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Exfoliation syndrome (XFS) is an age-related systemic disorder characterized by excessive production and progressive accumulation of abnormal extracellular material, with pathognomonic ocular manifestations. It is the most common cause of secondary glaucoma, resulting in widespread global blindness. We performed Transcriptomic Wide Association Studies using PrediXcan models trained in 48 GTEx tissues to identify genetically-determined gene expression changes associated with XFS risk, leveraging on results from a global GWAS that included 123,457 individuals from 24 countries. Twenty-eight genes in the chr15q22-25 region showed statistically significant associations in both single-tissue and multi-tissue analysis. Reduced models for these genes that excluded variants in LD with the known LOXL1 signal showed genome-wide significant association signals in nine genes, independently of LOXL1. Out of these ten genes, mRNA transcript levels for ARID3B, CD276, LOXL1, NEO1, SCAMP2, and UBL7 were significantly decreased in iris tissues from XFS patients compared to control samples. Genes with genetically determined expression changes in XFS were significantly enriched for genes associated with inflammatory conditions. We further explored the health consequences of high susceptibility to XFS using a large electronic health record and observed a higher incidence of XFS comorbidity with inflammatory and connective tissue diseases. Our results implicate a role for connective tissues and inflammation in the etiology of XFS. Targeting the inflammatory pathway may be a potential therapeutic option to reduce progression in XFS.

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“…84,85 The association with inflammation is consistent with studies in limited numbers of XFS patients that found elevated inflammatory markers relative to controls, including cytokines, and markers such as interleukin-6 (IL-6) and IL-8, 86,87 tumor necrosis factor-α (TNF-α) and YKL-40. 88,89 However, there are conflicting results for high sensitivity C-reactive protein. 90,91 In addition, the XFS gene sets are enriched for genes that map to variants implicated in coffee and caffeine intake.…”

Section: Comorbidity/pleiotropy Analysismentioning

confidence: 99%

Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Exfoliation Syndrome

Hirbo¹,

Pasutto

Gamazon

et al. 2020

Preprint

View full text Add to dashboard Cite

Exfoliation syndrome (XFS) is an age-related systemic disorder characterized by excessive production and progressive accumulation of abnormal extracellular material, with pathognomonic ocular manifestations. It is the most common cause of secondary glaucoma, resulting in widespread global blindness. We performed Transcriptomic Wide Association Studies (TWAS) using PrediXcan models trained in 48 GTEx tissues to identify genetically- determined gene expression changes associated with XFS risk, leveraging on results from a global GWAS that included 123,457 individuals from 24 countries. We observed twenty-eight genes in a three-Megabase chr15q22-25 region that showed statistically significant associations, which were further whittled down to ten genes after additional statistical validations. In experimental analysist of these ten genes, mRNA transcript levels for ARID3B, CD276, LOXL1, NEO1, SCAMP2, and UBL7 were significantly decreased in iris tissues from XFS patients compared to control samples. Genes with genetically determined expression changes in XFS were significantly enriched for genes associated with inflammatory conditions. We further explored the health consequences of high susceptibility to XFS using a large electronic health record and observed a higher incidence of XFS comorbidity with inflammatory and connective tissue diseases. Our results implicate a role for connective tissues and inflammation in the etiology of XFS. Targeting the inflammatory pathway may be a potential therapeutic option to reduce progression in XFS.

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YKL-40 is a local marker for inflammation in patients with pseudoexfoliation syndrome

Cited by 6 publications

References 37 publications

Analysis of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome

Analysis of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome

Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Etiology of Exfoliation Syndrome

Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Exfoliation Syndrome

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