SNPwatch: AMD Linked to Yet Another Immune System Gene

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world among people over 60. The two forms of the disease – wet and dry – both cause vision loss by destroying cells in the central portion of the retina.

In the last few years, progress in understanding AMD has been made thanks in part to the discovery of several common genetic variants, or SNPs, that together explain a large part of the risk for the disease. Several of these recently discovered AMD SNP associations have pointed to a role for the immune system in the disease.

A new study published online Monday in The Lancet yet again links the immune system to AMD. As is the case for several of the previously found SNPs, the variant found in this study is in a gene involved in the complement pathway, an arm of the immune system that facilitates the elimination of both pathogens and cellular debris.

Many years ago some researchers suspected that the complement system might be involved in AMD. Proteins from this pathway were found in drusen, the small crystalline deposits that build up in the eyes of people with AMD. But it was not until genetic studies started to show a link between AMD and complement genes that other scientists began to sit up and take notice.

In two separate samples — one British with 479 AMD patients and 479 controls, the other from the U.S. with 248 cases and 252 controls — Ennis et al found that the odds of developing AMD were reduced for every A T a person had at SNP rs2511989. Those with one A T had 0.68 times the odds of people with the GG CC genotype, and people with two As Ts had 0.44 times the odds.

(23andMe customers can check their data for rs2511989 using the Browse Raw Data feature. Note: The original post talked about As and Gs.  But our Browse Raw Data actually gives the data in terms of Ts and Cs.  Two different ways of looking at the same thing!  Sorry for the confusion!)

SNP rs2511989 is in the SERPING1 gene, which encodes a protein that regulates the complement pathway.

“Our findings add to the growing understanding of the genetics of age-related macular degeneration, which should ultimately lead to novel treatments for this common and devastating disease,” the authors write.

In an accompanying comment in The Lancet, Caroline Klaver and Arthur Bergen, two scientists not associated with the research, said the results of Ennis et al need to be replicated in large, independent samples before SERPING1 will be established as a true risk factor for AMD. They also suggest that the researchers may find other SNPs within the gene that are even more tightly linked to AMD.