In:
Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-05-23)
Kurzfassung:
Although lysyl oxidase-like 1 ( LOXL1 ) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C 〉 G transversion exerts a cis -acting effect on the expression levels of LOXL1 , mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1 , eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.
Materialart:
Online-Ressource
ISSN:
2041-1723
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2017
ZDB Id:
2553671-0