Not everyone is thrilled by the arrival of spring – for an increasing number of people, blooming trees and flowers signal the beginning of allergy season. One of the most common symptoms is atopic dermatitis, also known as eczema – a recurring, itchy rash that can be triggered by pollen, food, or other environmental factors. Studies have shown that this dermititis runs in families, but it has been difficult to link the problem to specific genes. Now researchers at the MDC, the Charité University Hospital, the Christian-Albrecht University of Kiel, and several other collaborating laboratories have connected a region of human chromosome 11 to an increased risk of developing eczema. The finding is an important step toward learning why the symptoms appear and hints at a connection between dermatitis and other diseases. The study was published on-line in the April 6 issue of Nature Genetics.
The study was carried out by researchers from the Berlin institutes and about a dozen other laboratories throughout Europe. They examined DNA from several thousand individuals and families from Europe, trying to find differences between the genes of people with symptoms and those of their unaffected family members and control groups. The goal was to find a pattern that consistently appeared only in people with eczema.
Sometimes a disease can be linked to a single "spelling variation" in a gene. Here that was not the case, says Young-Ae Lee of the MDC, a lead researcher on the study. "Instead, we found several different spellings consistently linked to dermititis – many of them occurring within a particular region of DNA on chromosome 11. These are normal sequence variants found quite commonly in Europe; we estimate that about 13 percent of the community has two copies of the variant that we have linked to the disease."
This region of chromosome 11 contains two genes – sequences which encode proteins – including a molecule called C11orf30. The problem may lie with this gene, Lee says, or with nearby DNA sequences. More research will be necessary to be sure. One aim of that work will be to discover the functions of the protein that C11orf30 encodes.
Researchers have recently traced another condition called Crohn's disease to the same region of the genome. Here patients have problems with the bowel rather than the skin, but there are similarities to dermatitis: Crohn's disease is accompanied by inflammations of the lining of the gut, and there is a drop in the body's ability to fight off bacteria.
"The skin and the gut lining both develop from epithelial cells," Lee says. "That makes two diseases with similar features that point to the same region of the genome. It suggests that C11orf30 is involved in the growth and development of epithelial cells. Cancer studies provide a third piece of evidence: Some breast and ovary tumors are triggered by defects in epithelial cells. In these patients, you often find extra copies of C11orf30. So our finding uncovers a red thread that gives us a new way of looking at all three of these problems, because they may be based on similar mechanisms."
The study uncovered several more links between atopic dermatitis and genes on other chromosomes. "These data suggest that additional low-risk factors remain to be discovered for the disease," Lee says. "Identifying them and their contributions will require expanding the study to larger patient groups."
Esparza-Gordillo et al.. Nature Genetics. 2009. 41: 596 – 601. Published online: 6 April.