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Psoriasis vulgaris, fetal growth, and genomic imprinting
H Traupe1, P J van Gurp, R Happle
1Department of Human Genetics, University of Nijmegen, The Netherlands.
Insights
Genomic imprinting, an epigenetic modification, influences psoriasis vulgaris. Psoriasis predisposition may be inherited differently based on the affected parent
Area of Science:
- Genetics
- Epigenetics
- Dermatology
Background:
- Psoriasis vulgaris is a common chronic inflammatory skin disease.
- The genetic basis of psoriasis involves multiple genes, but major predisposing genes are not fully understood.
- Genomic imprinting, where gene expression depends on parental origin, is a known epigenetic phenomenon.
Purpose of the Study:
- To investigate potential genomic imprinting of a major susceptibility gene for psoriasis vulgaris.
- To explore the influence of parental sex on disease inheritance and manifestation.
- To understand the role of epigenetic modifications in psoriasis pathogenesis and clinical course.
Main Methods:
- Analysis of birth weight differences in offspring based on the sex of the psoriatic parent.
- Assessment of disease penetrance in offspring according to the sex of the affected parent or gene carrier.
- Statistical evaluation of observed inheritance patterns compared to expected Mendelian distributions.
Main Results:
- Children born to fathers with psoriasis were significantly heavier than those born to mothers with psoriasis (270 g difference, P < 0.004).
- Offspring of affected fathers or male gene carriers showed significantly higher rates of psoriasis manifestation compared to offspring of affected mothers or female gene carriers (P < 0.015 and P < 0.007).
- Analysis of 91 grandchildren revealed a significant deviation from expected inheritance, with 65% having an affected grandfather versus 35% a psoriatic grandmother (P < 0.04).
Conclusions:
- Two independent lines of evidence suggest genomic imprinting of a major psoriasis vulgaris susceptibility gene.
- Parental sex influences both birth weight and disease penetrance in psoriasis.
- Epigenetic modifications, specifically genomic imprinting, may contribute to the variable clinical activity and unpredictable course of psoriasis.
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.