Filaggrin loss-of-function mutations as risk factors for ischemic stroke in the general population.

Essentials FLG mutations cause atopic dermatitis, previously found to be associated with ischemic stroke. Association between FLG mutations and ischemic stroke was examined in 97 174 Danish individuals. FLG mutations were associated with increased ischemic stroke risk in the general population. The association was most pronounced in younger individuals, and in current and former smokers. SUMMARY: Background Heritability studies have shown a considerable genetic component to ischemic stroke risk; however, much is unknown as to which genes are responsible. Also, previous studies have found an association between atopic dermatitis and increased ischemic stroke risk. Objective To test the hypothesis that FLG loss-of-function mutations, known to be associated with atopic dermatitis, were also associated with ischemic stroke. Methods A total of 97 174 individuals, with 3597 cases of ischemic stroke, from the Copenhagen General Population Study, the Copenhagen City Heart Study and the Copenhagen Carotid Stroke Study were genotyped for the two most common filaggrin mutations, FLG R501X and FLG 2282del4. Results FLG mutation carriers had an odds ratio for ischemic stroke of 1.15 (95% confidence interval [CI], 1.02-1.30) compared with non-carriers. Risk of ischemic stroke for FLG mutation carriers was higher among individuals aged < 50 years, with an odds ratio of 1.72 (1.11-2.67), compared with non-carriers. When stratified for smoking, ischemic stroke risk was primarily seen in current and former smokers, with an odds ratio of 1.25 (1.08-1.44). FLG mutations were not associated with conventional cardiovascular risk factors except for slightly more pack-years smoked among mutation carriers, but were associated with increased risk of self-reported eczema, with an odds ratio of 1.42 (1.32-1.52). Finally, self-reported eczema was associated with increased ischemic stroke risk, with an age and sex adjusted hazard ratio of 1.24 (1.01-1.52); however, the association was not statistically significant after multifactorial adjustment. Conclusion In this study of 97 174 individuals from the Danish general population, FLG loss-of-function mutations were associated with increased ischemic stroke risk; however, residual confounding is a possibility.

Disminución de triglicéridos sin ayuno y reducción de mortalidad por cualquier causa: un estudio de randomización mendeliana / Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study

Antecedentes: El aumento de los triglicéridos plasmáticos sin ayuno, marcador del aumento de colesterol en lipoproteínas remanentes, es un importante factor de riesgo para enfermedad cardiovascular, pero se desconoce si la reducción en las concentraciones de triglicéridos, sobre una base genética, a lo largo de toda la vida en última instancia conduce a una menor mortalidad por cualquier causa. Pusimos a prueba esta hipótesis. Métodos: Estudiando individuos del Copenhagen City Heart Study en un diseño de randomización mendeliana, en primer lugar estudiamos si las menores concentraciones de triglicéridos sin ayuno se asociaron con una reducción de mortalidad por cualquier causa en un análisis observacional (n=13.957); segundo, si variantes genéticas en la enzima hidrolizante de triglicéridos lipoproteína lipasa, que resultan en reducción de los triglicéridos plasmáticos sin ayuno y del colesterol de remanentes, se asociaron con una reducción de mortalidad por cualquier causa (n=10.208). Resultados...

Background: Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all-cause mortality is unknown. We tested this hypothesis. Methods: Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). Results...

In situ and invasive squamous cell carcinoma of the vulva in Denmark 1978-2007-a nationwide population-based study.

OBJECTIVE: To determine the incidence of vulvar carcinoma in situ (CIS) and cancer of squamous cell (SC) origin in Denmark in the period 1978-2007. METHODS: Using the nationwide Danish Cancer Registry, we identified 980 women diagnosed with vulvar CIS 1978-2003 (67.8% were SC) and 2455 women diagnosed with vulvar cancer 1978-2007 (76.0% were SC). Analysis was restricted to vulvar CIS and cancer of SC origin. We assessed age-specific incidence rates, age-standardized incidence rates, and distribution of stage at diagnosis. Poisson regression analysis was used to estimate the average annual percentage change. RESULTS: During the study period the age-standardized incidence rate of vulvar SC CIS increased by 1.97% per year (95% CI: 0.99% to 2.96%) with a tendency toward a steeper increase among women younger than 50 years. The age-standardized incidence rate of vulvar SC cancer showed a stable or slightly increasing pattern. However, among women below 60 years of age a significantly increasing trend was observed (1.60% per year; 95% CI: 0.50% to 2.71%). The distribution in the extent of vulvar SC cancer at diagnosis showed a tendency toward a higher proportion being diagnosed with localized disease in the more recent calendar years. CONCLUSIONS: The incidence rates of vulvar SC CIS and vulvar SC cancer among women below the age of 60 years have increased since 1978. Human papillomavirus (HPV) could explain the increase and thus, the recent introduction of HPV vaccination may in the future result in a notable reduction of vulvar malignancies.