Psoriasis Carries an Increased Risk of Venous Thromboembolism: A Danish Nationwide Cohort Study

Psoriasis is an immunoinflammatory disease associated with cardiovascular risk factors, atherothrombotic events, and hypercoagulability. Venous thromboembolism (VTE) is potentially lethal and shares risk factors with psoriasis, but the risk of VTE associated with psoriasis is unknown. The present study investigated the potential association between psoriasis and VTE.Information from nationwide prospectively recorded registers of hospitalization, drug dispensing from pharmacies, socio-economic data, and causes of death was linked on an individual level. In an unselected nationwide cohort, we used multivariate Poisson regression models controlling for age, gender, comorbidity, concomitant medication, socio-economic data, and calendar year, to assess the risk of VTE associated with psoriasis. A total of 35,138 patients with mild and 3,526 patients with severe psoriasis were identified and compared with 4,126,075 controls. Patients with psoriasis had higher incidence rates per 1000 person-years of VTE than controls (1.29, 1.92, and 3.20 for controls, mild psoriasis, and severe psoriasis, respectively). The rate ratio (RR) of VTE was elevated in all patients with psoriasis with RR 1.35 (95% confidence interval [CI] 1.21–1.49) and RR 2.06 (CI 1.63–2.61) for mild and severe psoriasis, respectively. Exclusion of patients with malignancies, and censoring of patients undergoing surgery did not alter the results.This nationwide cohort study indicates that patients with psoriasis are at increased risk of VTE. The risk was highest in young patients with severe psoriasis. Physicians should be aware that patients with psoriasis may be at increased risk of both venous and arterial thromboembolic events

Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency

BACKGROUND: Infants are vulnerable to zinc deficiency. Thus, abnormally low breast milk zinc levels cause transient neonatal zinc deficiency (TNZD) in breast-fed infants. TNZD has been considered to be rare because of a paucity of citations in the published literature. However, recent studies of affected mothers identified four missense mutations in the solute carrier family 30 member 2 gene (SLC30A2), which encodes the zinc transporter, ZnT2. METHODS: Genetic analyses of SLC30A2/ZnT2 in three Japanese mothers secreting low-zinc milk (whose infants developed TNZD) were performed. The effects of identified mutations were examined in a cell-based assay. Furthermore, 31 single-nucleotide polymorphisms (SNPs) in SLC30A2/ZnT2 were evaluated for their potential involvement in low-zinc levels in milk. RESULTS: Each mother had a different novel heterozygous mutation in SLC30A2/ZnT2. One mutation reduced splicing efficiency of the SLC30A2/ZnT2 transcript, and all ZnT2 mutants were defective in zinc transport and were unstable in cells. Moreover, four SNPs caused a significant loss of zinc-transport activity, similar to that in disease-causing ZnT2 mutants. CONCLUSION: Our results indicate that many SLC30A2/ZnT2 mutations cause or potentially cause TNZD. Genetic information concerning TNZD pathogenesis is limited, and our results suggest that the TNZD frequency may be higher than previously thought