Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Merle, DA; Sen, M; Armento, A; Stanton, CM; Thee, EF; Meester-Smoor, MA; Kaiser, M; Clark, SJ; Klaver, CCW; Keane, PA; Wright, AF; Ehrmann, M; Ueffing, M.
10q26 - The enigma in age-related macular degeneration.
Prog Retin Eye Res. 2023; 96: 101154
Doi: 10.1016/j.preteyeres.2022.101154
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Merle David Adrian
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- Abstract:
- Despite comprehensive research efforts over the last decades, the pathomechanisms of age-related macular degeneration (AMD) remain far from being understood. Large-scale genome wide association studies (GWAS) were able to provide a defined set of genetic aberrations which contribute to disease risk, with the strongest contributors mapping to distinct regions on chromosome 1 and 10. While the chromosome 1 locus comprises factors of the complement system with well-known functions, the role of the 10q26-locus in AMD-pathophysiology remains enigmatic. 10q26 harbors a cluster of three functional genes, namely PLEKHA1, ARMS2 and HTRA1, with most of the AMD-associated genetic variants mapping to the latter two genes. High linkage disequilibrium between ARMS2 and HTRA1 has kept association studies from reliably defining the risk-causing gene for long and only very recently the genetic risk region has been narrowed to ARMS2, suggesting that this is the true AMD gene at this locus. However, genetic associations alone do not suffice to prove causality and one or more of the 14 SNPs on this haplotype may be involved in long-range control of gene expression, leaving HTRA1 and PLEKHA1 still suspects in the pathogenic pathway. Both, ARMS2 and HTRA1 have been linked to extracellular matrix homeostasis, yet their exact molecular function as well as their role in AMD pathogenesis remains to be uncovered. The transcriptional regulation of the 10q26 locus adds an additional level of complexity, given, that gene-regulatory as well as epigenetic alterations may influence expression levels from 10q26 in diseased individuals. Here, we provide a comprehensive overview on the 10q26 locus and its three gene products on various levels of biological complexity and discuss current and future research strategies to shed light on one of the remaining enigmatic spots in the AMD landscape.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Serine Endopeptidases - genetics, metabolism
- Genome-Wide Association Study - administration & dosage
- Proteins - genetics, metabolism
- Macular Degeneration - genetics, metabolism
- Gene Expression Regulation - administration & dosage
- Polymorphism, Single Nucleotide - administration & dosage
- Genotype - administration & dosage
- Genetic Predisposition to Disease - administration & dosage
- Find related publications in this database (Keywords)
- Age-related macular degeneration (AMD)
- 10q26 risk locus
- PLEKHA1
- ARMS2
- HTRA1
- Extracellular matrix (ECM)