The chromosome 10q26 susceptibility locus in age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Two major risk loci for the disease have been identified: CFH on chromosome 1 and a locus in chromosomal region 10q26. The CFH association clearly implicates the alternative complement pathway in disease, but the chr10q26 locus, spanning the ARMS2 and HTRA1 genes, is the subject of controversy. High linkage disequilibrium in this region prevents elucidation of the causal variant or even which gene influences AMD susceptibility. There are conflicting reports of alterations in transcript or protein levels of both ARMS2 and HTRA1 in AMD, so the issue remains unresolved. In this chapter, HTRA1 - a serine protease with known roles in extracellular matrix (ECM) degradation and TGF ® signalling - is evaluated as a candidate gene for regulating susceptibility in AMD. © 2012 Springer Science+Business Media, LLC.