Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration

Abstract

Author Summary Age-related macular degeneration (AMD) is the leading blindness cause in western countries. Several genes encoding components of the complement pathway—including CFH, C2/BF, and C3 —have been confirmed to be associated with AMD, as well as a region on 10q26 that encompasses two genes. Recent data have suggested that loss of LOC387715 on 10q26, mediated by an insertion/deletion (in/del) at its 3'UTR that destabilizes its message, is causally related with the disorder. We found that a common disease haplotype including the in/del and rs11200638 also has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. We propose a binary model where downregulation of LOC387715 and concomitant upregulation of HTRA1 best explain the risk associated with the 10q26 AMD region.