Macular retinal thickness differs markedly in age-related macular degeneration driven by risk polymorphisms on chromosomes 1 and 10

Autor:	Burt Richards, Gregory S. Hageman, Moussa A. Zouache, Jill L. Hageman, Christian Matthew Pappas, Alex Bennion
Rok vydání:	2020
Předmět:	0301 basic medicine Male medicine.medical_specialty genetic structures Disease Polymorphism Single Nucleotide Article Retina 03 medical and health sciences chemistry.chemical_compound Macular Degeneration 0302 clinical medicine Disease severity Age related Ophthalmology Genetics research Medicine Humans Clinical genetics Author Correction Aged Aged 80 and over Multidisciplinary Disease genetics business.industry Chromosomes Human Pair 10 Haplotype Chromosome Proteins Retinal Complement System Proteins High-Temperature Requirement A Serine Peptidase 1 Macular degeneration Middle Aged medicine.disease eye diseases 030104 developmental biology chemistry Chromosomes Human Pair 1 Complement Factor H HTRA1 030221 ophthalmology & optometry Female sense organs business
Zdroj:	Scientific Reports
ISSN:	2045-2322
Popis:	The two most common genetic contributors to age-related macular degeneration (AMD), a leading cause of irreversible vision loss worldwide, are variants associated with CFH-CFHR5 on chromosome 1 (Chr1) and ARMS2/HTRA1 on chromosome 10 (Chr10). We sought to determine if risk and protective variants associated with these two loci drive differences in macular retinal thickness prior and subsequent to the onset of clinically observable signs of AMD. We considered 299 individuals (547 eyes) homozygous for risk variants or haplotypes on Chr1 or Chr10 exclusively (Chr1-risk and Chr10-risk, respectively) or homozygous for a neutral haplotype (Chr1-neu), for the protective I62 tagged haplotype (Chr1-prot-I62) or for the protection conferring CFHR3/1 deletion haplotype (Chr1-prot-del) on Chr1 without any risk alleles on Chr10. Among eyes with no clinically observable signs of AMD, the deletion of CFHR3/1, which is strongly protective against this disease, is associated with significantly thicker retinas in the perifovea. When controlling for age, Chr10-risk eyes with early or intermediate AMD have thinner retinas as compared to eyes from the Chr1-risk group with similar disease severity. Our analysis indicates that this difference likely results from distinct biological and disease initiation and progression events associated with Chr1- and Chr10-directed AMD.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d2f5d1b208fdef7845880b66b89c72b https://pubmed.ncbi.nlm.nih.gov/34021232 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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