The interrelationship between sex, susceptibility factors, and outcome in ankylosing spondylitis and its associated disorders including inflammatory bowel disease, psoriasis, and iritis

Abstract

Objective: To examine the evidence that families, where the mother has disease, carry more heritable factors and investigate the effect of maternal/paternal inheritance on phenotypic expression of disease in terms of (a) severity and outcome and (b) additional co-disorders. The children of women with ankylosing spondylitis (AS) develop the disease more often than the children of men. This suggests that either women with disease carry more susceptibility factors than men or that the uterine environment/breast feeding may play a role in AS.

Methods: The number of second degree relatives (i.e., grandparent, aunt/uncle) was calculated for those index patients with a mother with disease as opposed to a father. Outcome measures were compared and prevalence of secondary disorders (i.e., psoriasis, iritis, inflammatory bowel disease) was examined in patients with an AS mother as opposed to an AS father.

Results: The affected offspring of maternal cases had more second degree relatives with disease [20% vs 9%, respectively, p = 0.012, odds ratio (OR): 2.3, 95% confidence interval (CI): 1.2, 4.5] than did children of affected men. The affected children of a mother with AS were comparable in terms of disease activity, function, and radiology to children of a father with disease. Inflammatory bowel disease was more prevalent among children of AS mothers than AS fathers (15% vs 5%, respectively, p = 0.009, OR: 2.9, 95% CI: 1.3, 6.3). Psoriasis was less prevalent among sons of AS mothers than among sons of AS fathers (9% vs 22%, respectively, p = 0.03, OR: 0.4, 95% CI: 0.2, 0.9).

Conclusion: The inherited susceptibility load is strongly linked to the sex of the parent with AS. Women with disease carry higher heritability (which is associated with inflammatory bowel disease) than do men. There is a male sex impact on susceptibility to psoriasis (when AS is present). However, there is no evidence that the susceptibility load has an effect on outcome or severity of disease (as measured by disease activity, function, and radiology), or that outcome is influenced by transmission of maternal as opposed to paternal factors.