Psoriasis vulgaris, fetal growth, and genomic imprinting

Abstract

We report on 2 independent lines of evidence suggesting genomic imprinting of a major gene for psoriasis vulgaris. First, the birth weight of children from psoriatics is influenced by the sex of the psoriatic parent. Children from fathers with psoriasis are considerably (270 g) heavier than children from mothers with psoriasis (P less than 0.004). Second, the disease manifestation (penetrance) depends in part on the sex of the psoriatic parent. Offspring from fathers with psoriasis and male "gene carriers" are significantly (P less than 0.015 and P less than 0.007) more often affected than offspring from mothers with psoriasis and female "gene carriers." Of 91 grandchildren with psoriasis 59 (65%) have an affected grandfather and 32 (35%) a psoriatic grandmother. This deviation from the expected distribution is significant (P less than 0.04). Genomic imprinting is considered a special case of epigenetic modification. We propose that epigenetic modifications of a major predisposing gene in somatic tissues could cause differences in disease activity of psoriasis and could account for the often unpredictable clinical course the disease takes.

Genetic epidemiology of psoriasis and psoriatic arthritis

“…14 The imprinting process, exemplified by the Prader-Willi syndrome, 14 allows gene expression from only the maternally or paternally derived chromosome. In one study, 11 the birthweight of children of parents with psoriasis was found to be influenced by the sex of the parent with psoriasis, with offspring of males with psoriasis weighing 270 g more than offspring of females with psoriasis. The same authors reanalysed the Faroe Island kindreds and noted a higher penetrance of psoriasis if the father was affected or a presumed gene carrier.…”

Epigenetic Manifestations in Diet-Related Disorders

“…It is thought that these nutrients have an ameliorating effect through either an antiproliferative or anti-inflammatory action. A parent-of-origin effect in families was reported by Traupe et al [30] who showed that the risk for the offspring is more often transmitted by affected or gene-carrying fathers than by mothers. In addition, significantly more index patients had an affected grandfather than an affected grandmother.…”

Unstable Phenotypes and Unstable DNA: A Relationship?

“…Genomic imprinting has recently been implicated in the genetics of psoriasis vulgaris, since children from fathers with psoriasis developed the disease far more often than children from psoriatic mothers [3]. Indeed, psoriasis vul garis is an unstable genetic disease par excellence, but we have forgotten to wonder about it.…”

“…Indeed, psoriasis vul garis is an unstable genetic disease par excellence, but we have forgotten to wonder about it. We have proposed that modification of the major predisposing gene in somatic tissue'could cause differences in disease activity of psoriasis and thus account for the often unpredictable cause of this unstable phenotype [3].…”