Psoriasis vulgaris, fetal growth, and genomic imprinting.

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.