Proteomics in Peyronie's Disease - including a review of gene profiling in PD

This article isn't published yet, the abstract is from an electronic preprint:

Is There a Role for Proteomics in Peyronie's Disea...[J Sex Med. 2007] - PubMed Result

...This review assesses the potential use of protein alterations measured by various novel technologies, to predict progression, regression, or stabilization of PD in an affected individual. Methods. A comprehensive literature review of the past decade in the field of gene profiling and protein expression of PD was performed...

As I wrote a couple of days ago, even an area as understudied as Peyronie's can advance quickly when new instruments are brought to bear on old questions. Proteomics is all the rage in our post-genomic era, but besides the faddish topic the article claims to have reviewed the full literature on gene profiling in PD (of course that probably took about 3 hours).

This is one article I'm going to have to drag out of the university library -- once it's published!

Peyronie's and chromosomal abnormalities

In my prior post I reviewed the OMIM entry on Peyronie's. That entry cited a 1987 and a 1991 (yeah, research is slow in this domain) article on chromosomal anomalies in the abnormal plaque tissue of the tunica albuginea found in Peyronie's disease.

These articles make the plaques seem more like a tumor than a conventional scar. Pubmed lets one query for "related articles" on a given topic, here's what that query looks like:

• Multiple clonal chromosome abnormalities in Peyronie's disease - 1991

One of the articles that turned up was interesting, emphases mine:

Mulhall JP et al. Chromosomal instability is de...[PMID: 14961053]

... Peyronie's disease is a fibrotic disorder, a condition characterized by cellular proliferation and excess extracellular matrix production. Previous work in related conditions has demonstrated chromosomal instability. This investigation was undertaken to analyze fibroblasts derived from Peyronie's disease tunical tissue for abnormalities of chromosome number and progression of cytogenetic aberrations during cell culture...

... Peyronie's disease plaque-derived fibroblasts demonstrated frequent aneusomies in chromosomes 7, 8, 17, 18 and X and recurrent deletions of chromosome Y. Peyronie's disease nonplaque tunica-derived fibroblasts demonstrated infrequent chromosomal changes early in culture; however, with repeated passaging the majority of cell cultures demonstrated aneusomies [ed: extra copies] in at least one chromosome. These data indicate that Peyronie's disease plaque-derived fibroblasts have consistent aneusomies even at early passage and that nonplaque tunica-derived cells from men with Peyronie's disease also demonstrate chromosomal instability. This suggests that the tunica albuginea of men with Peyronie's disease may be predisposed to undergoing unregulated fibrosis. These findings confirm the transformed nature of the Peyronie's disease tunical fibroblasts studied in this analysis. While the etiology of these findings is not clear, it is likely that these pathobiological characteristics contribute to the pathophysiology of this disease process.

In other words men who develop Peyronie's Disease have something wrong with all the cells of their "tunica albuginea", not only those involved in Peyronie's. Of course this implies there's something wrong with at least those cells everywhere in the body.

In particular the cells are prone to a crazed kind of fibrosis (tough fiber generation) instead of a reasoned, measured, sort of fibrotic reaction.

It would be interesting to know what other conditions this presumably genetic defect may predispose to -- besides Dupuytren's contracture.

From a science point of view, this study tells us something fairly interesting. There's very little active research in Peyronie's, but it's studied using tools that are developed for other, actively studied, domains. A competent researcher can simply repeat a study from 10 years ago, and by virtue of better tools new knowledge will emerge.

OMIM - The Peyronie Discussion

OMIM, the "online mendelian inheritance in man" NIH database, published out of Johns Hopkins, is a formidable reference source. The discussion of "Peyronie Disease", however, is a bit eccentric. For example: "An anonymous nongeneticist suggested to me in 1980 that Peyronie disease is 'sex-linked with reduced penetrance.'" Cough. That doesn't show up in most of the OMIM posts, I get a feeling this one is under-edited.

Even so, I've excerpted and bolded some sections.

OMIM - PEYRONIE DISEASE

... Bias et al. (1982) concluded that this phenotype is a male-limited, autosomal dominant trait. They traced Peyronie disease through several families. Dupuytren contracture was often present in both males and females. In 1 kindred, males in 3 successive generations had Peyronie disease and Dupuytren contractures, and the latter was present in a fourth generation. Close linkage with HLA (see 142800) was excluded. Chromosomal abnormalities were described by Somers et al. (1987) and by Guerneri et al. (1991).

In Rome, Carrieri et al. (1998) performed a case-control study of 134 men with Peyronie disease and 134 male controls. Men who had undergone invasive procedures on the penis (e.g., urethral catheterization, cystoscopy, and transurethral prostatectomy) had a 16-fold increased risk of Peyronie disease, while a nearly 3-fold increase was observed among men who had genital and/or perineal trauma. ...

... Dupuytren contracture was found in 21% of cases and none of the controls, and 4% of the cases and none of the controls reported familial history for Peyronie disease.

Note that the key research on the genetics of Peyronie's was done twenty-five years ago, and yet it's omitted from most discussions of the disorder (I'll be adding it to Wikipedia.) I was very surprised by the 16-fold increase with urethral catheterization.

If I were a urologist, I would routinely ask prior to any urologic procedure whether the patient had any relatives with Dupuytren's contracture. If they did, I'd reconsider the need for the procedure. A 16-fold increase is enormous.

It's most likely that Peyronie's Disease is a pathologic reaction to common micro-trauma of the penile vasculature. Men who don't carry* the gene may develop small scars or non-significant plaques, men who carry the gene* develop plaques and pathologic scarring.

* Genetics is far more complex than it once was. Now when we say "carry" we mean something like "a complex of interacting genetic material" with one or more interacting mutations.