Analysis Of HTRA1 Promoter Polymorphisms Implicated In AMD

Noriko Esumi, MD, PhD Johns Hopkins University


We are trying to determine how genes modify the risk of developing AMD. There is evidence that gene regulation is important, and we propose to study one aspect of this.

Project Details

What is the "big picture" question I am trying to address? Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among elderly people in the developed countries including the United States. Multiple genes and environmental factors seem to be involved in developing AMD, and geneticists have been making great progress towards finding such AMD-associated genes. Studies in a genome-wide scale identified a location on human chromosome 10 (specifically, 10q26) with the strongest evidence for linkage for an AMD susceptibility (risk) gene; however, the critical region on 10q26 is still controversial. Several research groups reported a sequence change in the predicted gene LOC387715 as the AMD-risk variant on chromosome 10q26, while other groups suggested another DNA sequence change, a G to A change located in the front of the HTRA1 gene, which leads to higher HTRA1 expression and thereby higher risk for AMD. Therefore, I am trying to resolve the controversy by clarifying whether the latter sequence change has any functional role leading to higher expression of the HTRA1 gene.