Session Type: Abstract Submissions (ACR)
Excessive paternal transmission has been previously documented in psoriatic disease. Our objective is to delineate the differential contributions of skin and joint manifestations to this ‘parent-of-origin’ effect, and determine whether the effect is differentially associated with psoriasis or PsA.
Parental history of PsA and/or psoriasis without arthritis was ascertained by questionnaire or during clinical assessment of PsA and psoriasis patients from two large cohorts. Data was combined with previously-published data. Proportions of maternal and paternal transmissions were compared using a normal approximation to the binomial distribution. Parental and patient phenotypes were resolved where possible into psoriasis alone or PsA and compared by chi-square test and logistic regression. Patients with paternally and maternally-transmitted disease were compared with respect to demographic and clinical characteristics as well as carriage of risk alleles at HLA-B, -C, –DR, –DQ, and MICA, using Student’s t-test or chi-square test.
We found a preponderance of patients with affected fathers compared to affected mothers in the combined analysis (397 [56%] versus 313 [44%], p=0.002). There was a greater excess of paternal transmissions in patients with a parental history of psoriasis (223 [58%] versus 162 [42%], p=0.002) compared to patients with a parental history of PsA (75 [54%] versus 65 [46%], p=0.45), but no difference in frequencies between these patients (p=0.37). Although the parent-of-origin effect also appeared to be stronger in PsA than in psoriasis patients, paternal history of psoriasis could not predict PsA. PsA patients with paternally-transmitted psoriasis had fewer damaged joints than patients with maternally-transmitted psoriasis (mean damaged joint count 6.3 compared to 12.9, p=0.04), and PsA patients with paternally-transmitted PsA had an earlier age of PsA diagnosis than patients with maternally-transmitted PsA (mean age 32.8 compared to 37.5 years, p=0.05). In one particular cohort, PsA patients with paternally-transmitted psoriasis had lower carriage rates of HLA-B*38 (p=0.006), HLA-C*06 (p=0.03), and MICA-129Met (p=0.01).
We have provided additional evidence of a parent-of-origin effect in psoriatic disease, which may be driven by paternal transmission of psoriasis without arthritis and may be characterized by an earlier-onset yet milder disease that is not associated with several known risk alleles in the MHC.
A. A. P. Rahman,
D. D. Gladman,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/contributions-of-skin-and-joint-manifestations-to-the-parent-of-origin-effect-in-psoriatic-disease/