Glucocorticoid receptor gene polymorphisms are associated with disease course during pregnancy and the post-partum period in rheumatoid arthritis

R A M Quax; Man Y A de; J W Koper; S P Willemsen; S W J Lamberts; J M W Hazes; R J E M Dolhain; R A Feelders

P188

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Endocrine Abstracts (2011) 26 P188

ECE2011 Poster Presentations Neuroendocrinology (36 abstracts)

Glucocorticoid receptor gene polymorphisms are associated with disease course during pregnancy and the post-partum period in rheumatoid arthritis

R A M Quax ¹ , Y A de Man ² , J W Koper ¹ , S P Willemsen ³ , S W J Lamberts ¹ , J M W Hazes ² , R J E M Dolhain ² & R A Feelders ¹

Err

Author affiliations

¹Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; ²Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; ³Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Background: The mechanism underlying the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and the subsequent post-partum flare is incompletely understood. The glucocorticoid receptor (GR) polymorphisms Bcl1 and 9β are associated with an increased and decreased glucocorticoid sensitivity respectively. We examined the relation between carriership of these functional GR polymorphisms and disease course during pregnancy and post-partum in RA.

Methods: One hundred and forty participants of the PARA study (pregnancy-induced amelioration of rheumatoid arthritis), a prospective study investigating the natural improvement during pregnancy and the postpartum flare in women with RA, were studied. During pregnancy, patients were evaluated each trimester and post-partum at 4–6, 12 and 26 weeks using a standardized 28-joint count for swelling and pain. Disease activity was scored using the DAS28-CRP-3. All patients were genotyped for GR polymorphisms Bcl1 and 9β. Data were analyzed using a mixed linear model, comparing carriers of the minor allele with non-carriers of each polymorphism with respect to improvement during pregnancy and post-partum flare. The area under the curve (AUC) was calculated for both time periods, reflecting total disease activity.

Results: During pregnancy, carriers of the Bcl1 polymorphism had a lower disease activity compared to carriers of the 9β minor allele. These differences were most pronounced in patients treated with glucocorticoids. Non-carriers had a disease course between those of Bcl1 and 9β carriers. Post-partum, disease activity increased in carriers of the 9β polymorphism, whereas carriers of the Bcl1 minor allele had less RA reactivation. The AUC of disease activity in the post-partum period was significantly lower for Bcl1 carriers when compared with 9β carriers.

Conclusions: Functional GR polymorphisms may influence RA disease course during and directly after pregnancy. Carriers of the glucocorticoid-sensitive GR polymorphism BCl1 may benefit most from treatment with exogenous glucocorticoids.