Genetic anticipation in rheumatoid arthritis in Europe

Objective. To investigate whether there is evidence for genetic anticipatio n in rheumatoid arthritis (RA) in Europe. Methods. Cross sectional comparison of data from all affected parent-offspr ing Fairs identified among (1) the RA population attending our department a nd (2) a large cohort of families from RA probands with both parents alive recruited by the European Consortium on RA families (ECRAF) for association studies. Longitudinal comparison between probands with and without parenta l RA. We used prospectively collected data on disease activity, therapies, and radiological outcomes from our Dutch inception cohort of patients with early RA during the first 6 years of followup. Results. From a total of 683 Dutch and 170 European patients we identified 28 Dutch and 21 European parent-offspring pairs with RA. Probands with pare ntal RA had an earlier disease onset compared with affected parents (Dutch p < 0.002, European p < 0.0001). In Dutch patients: the prevalence of HLA-D R4, DR4 double dose, and shared epitope (SE) double dose was slightly highe r in probands with parental RA than in those without [odds ratios (95% CI) 2.0 (0.7-5.8), 2.79 (0.8-9.4), and 2.12 (0.6-8.7), respectively]. The same was true for European probands concerning SE double dose [OR (95% CI) 1.76 (0.6-8.7)]. No other relevant differences in demographic or clinical indice s were found between probands with affected parents and those without, Dise ase course (Disease Activity Score) and therapies used during the first 6 y ear of followup were similar in Dutch patients with and without parental RS I. Radiological damage at baseline was lower in the former group and this d ifference persisted after 3 and 6 years. Conclusion. Our data suggest that genetic anticipation in RA does occur in terms of an earlier disease onset in the offspring. Despite a slightly high er prevalence of HLA alleles encoding for the SE, probands with confirmed p arental RA had no worst outcome than those without.