Similar genes found in Dupuytren's and Peyronie's

Dupuytren's and Peyronie's disease are believed to be related, to share a common genetic starting point. This has been an assumption, not hard fact: the genetic starting points of these conditions are not yet known, much less known to be the same. Doctors have been wrong on these issues in the past: in the 1800's, it was an accepted "fact" that Dupuytren's and gout were related. They are not: the only relationship is demographic overlap. We now have better tools to find genetic similarities of Dupuytren's Disease (DD) and Peyronie's Disease (PD). All normal body processes are regulated and balanced by genetically controlled feedback loops: genes are upregulated (turned on) or downregulated (turned off) to maintain balance. DD and PD are the end effects of a broken feedback loop: an on switch is stuck in the on position, an off switch is stuck off, or both. One way to study up and down regulation is to use reverse transcriptase. Here's how it works. Genes are different molecules strung together into huge DNA molecules. When a gene is upregulated (turned on), it makes RNA molecules, which are like small, mirror images of itself. RNA carries orders from the boss DNA to control the rest of the cell. Reverse transcriptase is a laboratory technique which reverses this process, making DNA mirror images of RNA taken from living cells to find what genes the RNA came from - what genes are upregulated. In this study "Comparison of gene expression profiles between Peyronie’s disease and Dupuytren’s contracture" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2004_Qian_1570.pdf), this technique was used to identify upregulated and downregulated genes in Peyronie's, Dupuytren's and normal tissues. The result? Yes, DD and PD appear to be genetically related. The list of identified genes and their actions is reviewed in the article. More pieces of the puzzle, more steps closer to a cure.

RNA, Growth Factors and Dupuytren's

Sorting out the genetic basis of Dupuytren's is not simply a matter of finding out which genes are involved. The goal is to understand the biochemistry of exactly what these specific genes do to either start or fail to stop the process of Dupuytren's. Cell biology is always a domino like set of events with many steps. The DNA molecules in a cell's genes act as a template to make messenger RNA (mRNA), which travels from the cell's nucleus to its protein manufacturing factories (ribosomes), where the mRNA then acts as a template to string amino acids together to make proteins. Our bodies use some proteins, like collagen, as structural building material; other proteins, called cytokines, are used as currency of communication between cells, directing cells what to do. In this study, "Abnormal growth factor and cytokine expression in Dupuytren's contracture" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1993_Baird_1442.pdf), researchers analyzed the cytokines produced by mRNA in Dupuytren's tissue, and found abnormal activity of interleukin-1a, interleukin-1ß, transforming growth factor ß and basic fibroblast growth factor. This approach, linking genes with proteins, brings us a step closer to solving the puzzle of a cure.

Dupuytren's Genes

The hunt is on for the genetic basis of Dupuytren's. A interesting analysis of the chromosome patterns found in Dupuytren's tissue found a variety of genetic abnormalities and the unexpected finding that these variations were not found in the skin but were seen in areas of palmar fascia not usually involved with Dupuytren's. (full text: http://www.dupuytrenfoundation.org/DupPDFs/1988_Wurster-Hill_1091.pdf). Twenty years after this report, the hunt is still on with more sophisticated equipment, identification of involved genes closer but still elusive: http://dupuytrenfoundation.blogspot.com/2009/11/gene-expression-in-dupuytrens.html. Still, so many questions: is it determined by one or several genes? If, as widely believed, the trait is a dominant gene, why is Dupuytren's more common in people with blue eyes, the result of a recessive gene? Does the genetic effect only involve the palmar fascia or all fascia? Dupuytren's skips generations and often appears with no family history: is it a common spontaneous mutation, and if so, is it more common in those born to older parents? Some day, these questions will be answered. With persistence, some day, there will be a cure.