Atrial fibrillation in immigrant groups::a cohort study of all adults 45 years of age and older in Sweden

To study the association between country of birth and incident atrial fibrillation (AF) in several immigrant groups in Sweden. The study population included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was defined as having at least one registered diagnosis of AF in the National Patient Register. The incidence of AF in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence intervals (CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status. Compared to their Swedish-born counterparts, higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74 (1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67-2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05-1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men (HRs ≤ 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain), Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon and Iran), and among women from Nordic countries (except Finland), Southern Europe, Western Europe (except Germany), Africa, North America, Latin America, Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion, we observed substantial differences in incidence of AF between immigrant groups and the Swedish-born population. A greater awareness of the increased risk of AF development in some immigrant groups may enable for a timely diagnosis, treatment and prevention of its debilitating complications, such as stroke

MDM2 promotes p21(waf1/cip1) proteasomal turnover independently of ubiquitylation

The CDK inhibitor p21(waf1/cip1) is degraded by a ubiquitin-independent proteolytic pathway. Here, we show that MDM2 mediates this degradation process. Overexpression of wild-type or ring finger-deleted, but not nuclear localization signal (NLS)-deleted, MDM2 decreased p21(waf1/cip1) levels without ubiquitylating this protein and affecting its mRNA level in p53(–/–) cells. This decrease was reversed by the proteasome inhibitors MG132 and lactacystin, by p19(arf), and by small interfering RNA (siRNA) against MDM2. p21(waf1/cip1) bound to MDM2 in vitro and in cells. The p21(waf1/cip1)-binding-defective mutant of MDM2 was unable to degrade p21(waf1/cip1). MDM2 shortened the half-life of both exogenous and endogenous p21(waf1/cip1) by 50% and led to the degradation of its lysine-free mutant. Consequently, MDM2 suppressed p21(waf1/cip1)-induced cell growth arrest of human p53(–/–) and p53(–/–)/Rb(–/–)cells. These results demonstrate that MDM2 directly inhibits p21(waf1/cip1) function by reducing p21(waf1/cip1) stability in a ubiquitin-independent fashion